- Email: [email protected]
Advances in melanocyte and melanoma biology
Archives of Biochemistry and Biophysics 563 (2014) 1–3
Contents lists available at ScienceDirect
Archives of Biochemistry and Biophysics journal homepage: www.elsevier.com/locate/yabbi
Editorial
Advances in melanocyte and melanoma biology Mammalian melanocytes are the pigment producing cells in the skin, hair follicles and the eye. In the skin, they constitute a relatively minor population compared to keratinocytes. Their primary and the only function of these cells is thought to be the source of melanin pigment, which is dispensable since albinos can survive and flourish. However, the impact of melanocytic disorders – from defects in pigmentation (such as congenital albinism and acquired vitiligo) to lethal malignancies (melanoma) – on human health and well-being cannot be overstated. The purpose of this Special Issue of Archives of Biochemistry and Biophysics is to highlight the current state of knowledge in melanocyte biology and melanocytic disorders. ‘‘Advances in Melanocyte and Melanoma Biology’’ was the focus of 18th meeting of the Pan American Society for Pigment Cell Research, organized by us the Fall 2013 held at Madison, WI. Most of the authors invited to contribute to this Special Issue presented their research at this meeting. All manuscripts were put through a rigorous peer review that met high standards of this journal. Although mammalian pigmentation as phenotypic and genetic trait has been studied for long, biochemical studies on melanocytes were not possible until successful culture of pure population of human melanocytes almost 30 years ago. Following the molecular cloning of mammalian tyrosinase and identification of microphthalmia associated transcription factor MITF (the master regulator of melanocytes), interest in pigment cell biology has grown exponentially and continues to attract many talented researchers with a wide range of expertise. Increasing incidence of cutaneous melanoma, which arises from melanocytes, and the notorious therapy resistance of this melanocytic malignancy have propelled studies in pigment cell biology with added urgency. This Special Issue contains 9 reviews and 8 original articles covering a broad range of topics in biochemistry of melanocytes and melanoma. The issue opens with review articles that address the roles of molecules and signaling pathways that are critical for the development and the differentiated functions of melanocytes. These are followed by reviews on selected topics in melanoma development and biochemical mechanisms in melanoma survival and proliferation. The original research articles that follow provide a snapshot of various biochemical pathways and biophysical processes that are focus of active investigation due to their role in melanocyte and melanoma cell survival and proliferation. Pigmentation is a complex phenotype that is regulated by over 100 genes that encode a variety of proteins, including transcription factors, melanin biosynthesis enzymes, cell surface receptors and ion transporters. Mammalian melanocytes synthesize two forms of melanin- the dark brown/black eumelanin and the yellow–red pheomelanin. The melanocortin a-MSH stimulates eumelanin synthesis. It is now recognized that the signaling mechanism http://dx.doi.org/10.1016/j.abb.2014.09.003 0003-9861/Ó 2014 Elsevier Inc. All rights reserved.
activated by a-MSH and its receptor MC1R is the major regulator of human pigmentation. MC1R is a G-protein coupled receptor and signals by activating adenylyl cyclase to increase cAMP formation. MC1R is highly polymorphic and certain single nucleotide polymorphisms of MC1R are associated with red hair color, which is characterized by prevalence of pheomelanin and reduction of eumelanin. The MC1R red hair color variants is associated with increased melanoma risk. The article by Abdel-Malek et al. [1] is a comprehensive review on the role of MC1R in melanin pigmentation and the growing knowledge on the importance of this receptor in regulating the DNA damage response of melanocytes to UV and in susceptibility to melanoma development. This article also includes a discussion on the potential of this knowledge for melanoma chemoprevention. Biochemical events downstream of MC1R signaling in melanocytes are mediated by cyclic AMP and culminate in transcriptional activation of cAMP responsive genes including MITF. Despite its well-established and critical role in melanocyte development, survival and differentiation, the role of cAMP signaling and pigmentation in melanoma is not well understood. A recent investigation on the mechanisms of acquired resistance of melanoma to MAPK targeted therapies has rekindled interest in this pathway. In this context, the review article by Liu et al. [2] provides an integrated view of genes and pathways that play important roles both in melanocyte specification and maintenance and in melanoma formation and progression. The authors discuss the connection between normal and cancerous development and the potential of targeting developmental pathways for melanoma therapy. The article by Rodriguez and Setaluri [3] provides an up to date, and timely review on the biochemical mechanisms that regulate cAMP signaling in melanocytes and melanoma and mediate its crosstalk with MAPK signaling. As the master regulator of melanocyte biology, MITF has been the focus numerous biochemical and molecular biological investigations. Genetic alterations in MITF locus found in melanoma strongly support the notion that MITF acts as a lineage addiction oncogene in melanoma. The review article by Hsiao and Fisher [4] synthesizes our current understanding of the roles of MITF and pigmentation in melanoma. Ion transport across cellular membranes is critical for many biological processes, including pigmentation. Several ion transporter proteins have recently been shown to regulate pigmentation and defects in their function is associated with pigmentary disorders and melanoma. Bellono and Oancea [5] have put together an informative article listing melanocyte cell surface plasma membrane and intracellular melanosomal membrane localized ion transporters and critical evaluation of the literature on their role in pigmentation. Although it is common knowledge that both white men and women show the highest incidence of melanoma, differences in
2
Editorial / Archives of Biochemistry and Biophysics 563 (2014) 1–3
the incidence and outcomes between genders and molecular basis for such differences have not been well studied. In their article on this topic, Nostrati and Wei [6] examine the available evidence for contribution of complex interplay between sex hormones, the immune system and oxidative stress response and recently identified oncogenes on the Y chromosome. Oxidative stress and mitochondrial function are now well established to play crucial roles in nearly all aspects of melanoma, including its development, progression and drug resistance. The article by Liu-Smith et al. [7] provides an update on ROS in melanoma etiology and progression with special emphasis on the role of NADPH oxidases in ROS and the potential of its inhibition as a therapeutic strategy for melanoma. Mitochondria play a central role in metabolic homeostasis in melanoma cells. In their article, Theodosakis et al. [8] discuss the roles of mitochondria in melanoma response to therapy and the development of resistance, highlight the differences in mitochondrial function among melanoma subsets and discuss the potential for targeting mitochondrial function for clinical benefit. Discovery of small (microRNAs) and long non-coding RNAs (lncRNAs) as important regulators of gene expression and hence almost all biological processes is increasingly appreciated. Several miRNAs and a few lncRNAs have been implicated in melanocyte and melanoma biology. The article by Aftab and Perera [9] is an exhaustive review of literature on this expanding area of research in melanoma. In addition to reviewing their mechanisms of action in various aspects of melanoma biology, this article also provides a critical perspective on the potential of these non-coding RNAs as tools for diagnosis and prognosis and targets for treatment of melanoma. The original research articles in this Special Issue cover broadly 3 areas of melanocyte and melanoma biochemistry. These include (a) action of depigmenting agents on melanocyte stem cells, (b) effects and mechanisms of action of melanin precursors and treatment with different agents (such as a fisetin, a dietary flavonoid; methotrexate (MTX), a dihydrofolate reductase inhibitor; Tenovin-1, a small molecule inhibitor of class III histone deacetylase sirtuin 1) on melanoma cell survival, and (c) molecular mechanisms of modulation of MAPK signaling by microRNA; the effects MAPK signaling on expression chromatin remodeling complex proteins, and mechanism of action of MAGE proteins in regulation of gene expression. The article by Bonchak et al. [10] investigates the contribution of melanocyte stem cells in limiting the treatment efficacy of the depigmenting hydroquinone used to treating extensive vitiligo. They show that treatment with a combination of the USFDA approved hydroquinone MBEH with an aminotetralin 8-DPAT shows superior therapeutic efficacy due to targeting of complementary cell populations. A role for the precursors and products of melanin biosynthesis in melanoma has been proposed earlier, however, the detailed molecular mechanisms of action remain to be fully understood. The article by Slominski et al. [11] describes a novel mechanistic link between melanogenesis and HIF-1a in cellular metabolism in melanoma. The histone deacetylase SIRT1 has been implicated in several biological processes including cellular metabolism and stress response. Wilking et al. [12] investigated the role and mechanism of sirtuin SIRT1 in melanoma development and progression and provide data showing that inhibition of SIRT1 with a small molecule inhibitor Tenovin-1, decreases melanoma cell viability presumably through an increase in p53 protein and activity. Although MTX has been used for long as a cancer chemotherapeutic agent, it has not proved useful for melanoma. In the article by Nihal et al. [13], the authors exploited the ability of MTX act as an inhibitor of DNA methylation and provide evidence to support the concept that a combination therapy with methotrexate and interferon a induces significantly higher cell death due to up regulation of Fas death receptor and its ligand.
In a continuing series of studies on the effects of fisetin, a dietary flavonoid, Syed et al. [14] report that fisetin induced cytotoxicity and apoptosis is mediated in part by induction of ER stress. This study shows that although fisetin treatment results in activation of AMPK, both AMPK-dependent and AMPK-independent mechanisms are involved in the cytotoxicity induced by this agent. Differential expression of various miRNAss in melanocytes and melanoma have been reported. How these miRNAs contribute to melanoma development and progression is not fully understood. The article by Poenitzsch et al. [15] implicates miR-340 as a modulator of MAPK pathway in melanoma due its potential to target numerous MAPK mRNAs. Similarly, while it is now well established that activation of MAPK signaling as the driver for melanoma, the specific genes and mechanisms that MAPK signaling activates to drive proliferation of melanocytes are not well understood. The paper by Mehrotra et al. [16] describes the effect of MAPK activation on expression of chromatin remodeling proteins in melanoma cells. Since their discovery as testes-specific antigens activated in cancer and recognized by the immune system, the MAGE family cancer-testes antigens have been the focus of numerous studies that elaborated novel functions for these proteins. Through their interaction with a KAP1, MAGE has been shown to regulate gene expression in melanoma cells. In the article by Xiao et al. [17], the authors investigated the reasons for the different responses of genes to interaction of MAGE-KAP1 complex with their cognate KRAB domain containing zinc finger transcription factors. It is our hope that this Special Issue will serve as a timely and comprehensive source for recent advances in melanocyte and melanoma biology to both the experts and the newcomers in the field. (1) Melanocortins and the melanocortin 1 receptor, moving translationally towards melanoma prevention Zalfa A. Abdel-Malek, Viki B. Swope, Renny J. Starner, Leonid Koikov, Pamela Cassidy, Sancy Leachman (2) Developmental Pathways Activated in Melanocytes and Melanoma Jianglan Liu, Mizuho Fukunaga-Kalabis, Ling Li, Meenhard Herlyn (3) Cyclic AMP (cAMP) signaling in melanocytes and melanoma Carlos Iván Rodríguez, Vijayasaradhi Setaluri (4) The roles of Microphthalmia-associated Transcription Factor and pigmentation in melanoma Jennifer J. Hsiao, David E. Fisher (5) Ion transport in pigmentation Nicholas W. Bellono, Elena V. Oancea (6) Sex disparities in melanoma outcomes: The role of biology Adi Nostrati, Maria L. Wei (7) Updates of reactive oxygen species in melanoma etiology and progression Feng Liu-Smith, Ryan Dellinger, Frank L. Meyskens Jr (8) Mitochondrial function in melanoma Nicholas Theodosakis, Goran Micevic, Daniel P. Kelly, Marcus Bosenberg (9) The role of microRNAs and long non-coding RNAs in the pathology, diagnosis, and management of melanoma Muhammad N. Aftab, Marcel E. Dinger, Ranjan J. Perera Original articles
(10) Targeting melanocyte and melanoma stem cells by 8hydroxy-2-dipropylaminotetralin Jonathan Bonchak, Jonathan M Eby, Kristin A Willenborg, David Chrobak, Steven W Henning, Anna Krzywiec, Stephen L. Johnson, I. Caroline Le Poole
Editorial / Archives of Biochemistry and Biophysics 563 (2014) 1–3
(11) The role of melanogenesis in regulation of melanoma behavior: Melanogenesis leads to stimulation of HIF-1a expression and HIF-dependent attendant pathways Andrzej Slominski, Cezary Skobowiat, T-K. Kim, Anna Brozyna, Zorica Janjetovic, D.L.P. Brooks, W. Jozwicki, Tiffany Seagroves (12) SIRT1 deacetylase is overexpressed in human melanoma and its small molecule inhibition imparts anti-proliferative response via p53 activation Melissa J. Wilking, Chandra Singh, Minakshi Nihal, Weixiong Zhong, Nihal Ahmad (13) Methotrexate inhibits the viability of human melanoma cell lines and enhances Fas/Fas-ligand expression, apoptosis and response to interferon-alpha: rationale for its use in combination therapy Minakshi Nihala, Jianqiang Wua, Gary S. Wood (14) Involvement of ER stress and activation of apoptotic pathways in fisetin induced cytotoxicity in human melanoma Deeba N. Syed, Rahul K. Lall, Jean Christopher Chamcheu, Omar Haidar, Hasan Mukhtar
3
(15) MicroRNA-340 as a modulator of RAS-RAF-MAPK signaling in melanoma Ashley M. Poenitzsch Stronga, Vijayasaradhi Setaluria, Vladimir S. Spiegelman (16) Modulation of BRAHMA expression by the mitogenactivated protein kinase/extracellular signal regulated kinase pathway is associated with changes in melanoma proliferation Aanchal Mehrotra, Srinivas Vinod Saladi, Archit R. Trivedi, Shweta Aras, Huiling Qi, Ashika Jayanthy, Vijayasaradhi Setaluri, Ivana L. de la Serna (17) MAGE proteins regulate KRAB zinc finger transcription factors and KAP1 E3 ligase activity Tony Z. Xiao, Yewseok Suh, B. Jack, Longley. Hasan Mukhtar Vijayasaradhi Setaluri Department of Dermatology, University of Wisconsin, Madison, WI 53706, USA E-mail addresses: [email protected] (H. Mukhtar), [email protected] (V. Setaluri).
Contents lists available at ScienceDirect
Archives of Biochemistry and Biophysics journal homepage: www.elsevier.com/locate/yabbi
Editorial
Advances in melanocyte and melanoma biology Mammalian melanocytes are the pigment producing cells in the skin, hair follicles and the eye. In the skin, they constitute a relatively minor population compared to keratinocytes. Their primary and the only function of these cells is thought to be the source of melanin pigment, which is dispensable since albinos can survive and flourish. However, the impact of melanocytic disorders – from defects in pigmentation (such as congenital albinism and acquired vitiligo) to lethal malignancies (melanoma) – on human health and well-being cannot be overstated. The purpose of this Special Issue of Archives of Biochemistry and Biophysics is to highlight the current state of knowledge in melanocyte biology and melanocytic disorders. ‘‘Advances in Melanocyte and Melanoma Biology’’ was the focus of 18th meeting of the Pan American Society for Pigment Cell Research, organized by us the Fall 2013 held at Madison, WI. Most of the authors invited to contribute to this Special Issue presented their research at this meeting. All manuscripts were put through a rigorous peer review that met high standards of this journal. Although mammalian pigmentation as phenotypic and genetic trait has been studied for long, biochemical studies on melanocytes were not possible until successful culture of pure population of human melanocytes almost 30 years ago. Following the molecular cloning of mammalian tyrosinase and identification of microphthalmia associated transcription factor MITF (the master regulator of melanocytes), interest in pigment cell biology has grown exponentially and continues to attract many talented researchers with a wide range of expertise. Increasing incidence of cutaneous melanoma, which arises from melanocytes, and the notorious therapy resistance of this melanocytic malignancy have propelled studies in pigment cell biology with added urgency. This Special Issue contains 9 reviews and 8 original articles covering a broad range of topics in biochemistry of melanocytes and melanoma. The issue opens with review articles that address the roles of molecules and signaling pathways that are critical for the development and the differentiated functions of melanocytes. These are followed by reviews on selected topics in melanoma development and biochemical mechanisms in melanoma survival and proliferation. The original research articles that follow provide a snapshot of various biochemical pathways and biophysical processes that are focus of active investigation due to their role in melanocyte and melanoma cell survival and proliferation. Pigmentation is a complex phenotype that is regulated by over 100 genes that encode a variety of proteins, including transcription factors, melanin biosynthesis enzymes, cell surface receptors and ion transporters. Mammalian melanocytes synthesize two forms of melanin- the dark brown/black eumelanin and the yellow–red pheomelanin. The melanocortin a-MSH stimulates eumelanin synthesis. It is now recognized that the signaling mechanism http://dx.doi.org/10.1016/j.abb.2014.09.003 0003-9861/Ó 2014 Elsevier Inc. All rights reserved.
activated by a-MSH and its receptor MC1R is the major regulator of human pigmentation. MC1R is a G-protein coupled receptor and signals by activating adenylyl cyclase to increase cAMP formation. MC1R is highly polymorphic and certain single nucleotide polymorphisms of MC1R are associated with red hair color, which is characterized by prevalence of pheomelanin and reduction of eumelanin. The MC1R red hair color variants is associated with increased melanoma risk. The article by Abdel-Malek et al. [1] is a comprehensive review on the role of MC1R in melanin pigmentation and the growing knowledge on the importance of this receptor in regulating the DNA damage response of melanocytes to UV and in susceptibility to melanoma development. This article also includes a discussion on the potential of this knowledge for melanoma chemoprevention. Biochemical events downstream of MC1R signaling in melanocytes are mediated by cyclic AMP and culminate in transcriptional activation of cAMP responsive genes including MITF. Despite its well-established and critical role in melanocyte development, survival and differentiation, the role of cAMP signaling and pigmentation in melanoma is not well understood. A recent investigation on the mechanisms of acquired resistance of melanoma to MAPK targeted therapies has rekindled interest in this pathway. In this context, the review article by Liu et al. [2] provides an integrated view of genes and pathways that play important roles both in melanocyte specification and maintenance and in melanoma formation and progression. The authors discuss the connection between normal and cancerous development and the potential of targeting developmental pathways for melanoma therapy. The article by Rodriguez and Setaluri [3] provides an up to date, and timely review on the biochemical mechanisms that regulate cAMP signaling in melanocytes and melanoma and mediate its crosstalk with MAPK signaling. As the master regulator of melanocyte biology, MITF has been the focus numerous biochemical and molecular biological investigations. Genetic alterations in MITF locus found in melanoma strongly support the notion that MITF acts as a lineage addiction oncogene in melanoma. The review article by Hsiao and Fisher [4] synthesizes our current understanding of the roles of MITF and pigmentation in melanoma. Ion transport across cellular membranes is critical for many biological processes, including pigmentation. Several ion transporter proteins have recently been shown to regulate pigmentation and defects in their function is associated with pigmentary disorders and melanoma. Bellono and Oancea [5] have put together an informative article listing melanocyte cell surface plasma membrane and intracellular melanosomal membrane localized ion transporters and critical evaluation of the literature on their role in pigmentation. Although it is common knowledge that both white men and women show the highest incidence of melanoma, differences in
2
Editorial / Archives of Biochemistry and Biophysics 563 (2014) 1–3
the incidence and outcomes between genders and molecular basis for such differences have not been well studied. In their article on this topic, Nostrati and Wei [6] examine the available evidence for contribution of complex interplay between sex hormones, the immune system and oxidative stress response and recently identified oncogenes on the Y chromosome. Oxidative stress and mitochondrial function are now well established to play crucial roles in nearly all aspects of melanoma, including its development, progression and drug resistance. The article by Liu-Smith et al. [7] provides an update on ROS in melanoma etiology and progression with special emphasis on the role of NADPH oxidases in ROS and the potential of its inhibition as a therapeutic strategy for melanoma. Mitochondria play a central role in metabolic homeostasis in melanoma cells. In their article, Theodosakis et al. [8] discuss the roles of mitochondria in melanoma response to therapy and the development of resistance, highlight the differences in mitochondrial function among melanoma subsets and discuss the potential for targeting mitochondrial function for clinical benefit. Discovery of small (microRNAs) and long non-coding RNAs (lncRNAs) as important regulators of gene expression and hence almost all biological processes is increasingly appreciated. Several miRNAs and a few lncRNAs have been implicated in melanocyte and melanoma biology. The article by Aftab and Perera [9] is an exhaustive review of literature on this expanding area of research in melanoma. In addition to reviewing their mechanisms of action in various aspects of melanoma biology, this article also provides a critical perspective on the potential of these non-coding RNAs as tools for diagnosis and prognosis and targets for treatment of melanoma. The original research articles in this Special Issue cover broadly 3 areas of melanocyte and melanoma biochemistry. These include (a) action of depigmenting agents on melanocyte stem cells, (b) effects and mechanisms of action of melanin precursors and treatment with different agents (such as a fisetin, a dietary flavonoid; methotrexate (MTX), a dihydrofolate reductase inhibitor; Tenovin-1, a small molecule inhibitor of class III histone deacetylase sirtuin 1) on melanoma cell survival, and (c) molecular mechanisms of modulation of MAPK signaling by microRNA; the effects MAPK signaling on expression chromatin remodeling complex proteins, and mechanism of action of MAGE proteins in regulation of gene expression. The article by Bonchak et al. [10] investigates the contribution of melanocyte stem cells in limiting the treatment efficacy of the depigmenting hydroquinone used to treating extensive vitiligo. They show that treatment with a combination of the USFDA approved hydroquinone MBEH with an aminotetralin 8-DPAT shows superior therapeutic efficacy due to targeting of complementary cell populations. A role for the precursors and products of melanin biosynthesis in melanoma has been proposed earlier, however, the detailed molecular mechanisms of action remain to be fully understood. The article by Slominski et al. [11] describes a novel mechanistic link between melanogenesis and HIF-1a in cellular metabolism in melanoma. The histone deacetylase SIRT1 has been implicated in several biological processes including cellular metabolism and stress response. Wilking et al. [12] investigated the role and mechanism of sirtuin SIRT1 in melanoma development and progression and provide data showing that inhibition of SIRT1 with a small molecule inhibitor Tenovin-1, decreases melanoma cell viability presumably through an increase in p53 protein and activity. Although MTX has been used for long as a cancer chemotherapeutic agent, it has not proved useful for melanoma. In the article by Nihal et al. [13], the authors exploited the ability of MTX act as an inhibitor of DNA methylation and provide evidence to support the concept that a combination therapy with methotrexate and interferon a induces significantly higher cell death due to up regulation of Fas death receptor and its ligand.
In a continuing series of studies on the effects of fisetin, a dietary flavonoid, Syed et al. [14] report that fisetin induced cytotoxicity and apoptosis is mediated in part by induction of ER stress. This study shows that although fisetin treatment results in activation of AMPK, both AMPK-dependent and AMPK-independent mechanisms are involved in the cytotoxicity induced by this agent. Differential expression of various miRNAss in melanocytes and melanoma have been reported. How these miRNAs contribute to melanoma development and progression is not fully understood. The article by Poenitzsch et al. [15] implicates miR-340 as a modulator of MAPK pathway in melanoma due its potential to target numerous MAPK mRNAs. Similarly, while it is now well established that activation of MAPK signaling as the driver for melanoma, the specific genes and mechanisms that MAPK signaling activates to drive proliferation of melanocytes are not well understood. The paper by Mehrotra et al. [16] describes the effect of MAPK activation on expression of chromatin remodeling proteins in melanoma cells. Since their discovery as testes-specific antigens activated in cancer and recognized by the immune system, the MAGE family cancer-testes antigens have been the focus of numerous studies that elaborated novel functions for these proteins. Through their interaction with a KAP1, MAGE has been shown to regulate gene expression in melanoma cells. In the article by Xiao et al. [17], the authors investigated the reasons for the different responses of genes to interaction of MAGE-KAP1 complex with their cognate KRAB domain containing zinc finger transcription factors. It is our hope that this Special Issue will serve as a timely and comprehensive source for recent advances in melanocyte and melanoma biology to both the experts and the newcomers in the field. (1) Melanocortins and the melanocortin 1 receptor, moving translationally towards melanoma prevention Zalfa A. Abdel-Malek, Viki B. Swope, Renny J. Starner, Leonid Koikov, Pamela Cassidy, Sancy Leachman (2) Developmental Pathways Activated in Melanocytes and Melanoma Jianglan Liu, Mizuho Fukunaga-Kalabis, Ling Li, Meenhard Herlyn (3) Cyclic AMP (cAMP) signaling in melanocytes and melanoma Carlos Iván Rodríguez, Vijayasaradhi Setaluri (4) The roles of Microphthalmia-associated Transcription Factor and pigmentation in melanoma Jennifer J. Hsiao, David E. Fisher (5) Ion transport in pigmentation Nicholas W. Bellono, Elena V. Oancea (6) Sex disparities in melanoma outcomes: The role of biology Adi Nostrati, Maria L. Wei (7) Updates of reactive oxygen species in melanoma etiology and progression Feng Liu-Smith, Ryan Dellinger, Frank L. Meyskens Jr (8) Mitochondrial function in melanoma Nicholas Theodosakis, Goran Micevic, Daniel P. Kelly, Marcus Bosenberg (9) The role of microRNAs and long non-coding RNAs in the pathology, diagnosis, and management of melanoma Muhammad N. Aftab, Marcel E. Dinger, Ranjan J. Perera Original articles
(10) Targeting melanocyte and melanoma stem cells by 8hydroxy-2-dipropylaminotetralin Jonathan Bonchak, Jonathan M Eby, Kristin A Willenborg, David Chrobak, Steven W Henning, Anna Krzywiec, Stephen L. Johnson, I. Caroline Le Poole
Editorial / Archives of Biochemistry and Biophysics 563 (2014) 1–3
(11) The role of melanogenesis in regulation of melanoma behavior: Melanogenesis leads to stimulation of HIF-1a expression and HIF-dependent attendant pathways Andrzej Slominski, Cezary Skobowiat, T-K. Kim, Anna Brozyna, Zorica Janjetovic, D.L.P. Brooks, W. Jozwicki, Tiffany Seagroves (12) SIRT1 deacetylase is overexpressed in human melanoma and its small molecule inhibition imparts anti-proliferative response via p53 activation Melissa J. Wilking, Chandra Singh, Minakshi Nihal, Weixiong Zhong, Nihal Ahmad (13) Methotrexate inhibits the viability of human melanoma cell lines and enhances Fas/Fas-ligand expression, apoptosis and response to interferon-alpha: rationale for its use in combination therapy Minakshi Nihala, Jianqiang Wua, Gary S. Wood (14) Involvement of ER stress and activation of apoptotic pathways in fisetin induced cytotoxicity in human melanoma Deeba N. Syed, Rahul K. Lall, Jean Christopher Chamcheu, Omar Haidar, Hasan Mukhtar
3
(15) MicroRNA-340 as a modulator of RAS-RAF-MAPK signaling in melanoma Ashley M. Poenitzsch Stronga, Vijayasaradhi Setaluria, Vladimir S. Spiegelman (16) Modulation of BRAHMA expression by the mitogenactivated protein kinase/extracellular signal regulated kinase pathway is associated with changes in melanoma proliferation Aanchal Mehrotra, Srinivas Vinod Saladi, Archit R. Trivedi, Shweta Aras, Huiling Qi, Ashika Jayanthy, Vijayasaradhi Setaluri, Ivana L. de la Serna (17) MAGE proteins regulate KRAB zinc finger transcription factors and KAP1 E3 ligase activity Tony Z. Xiao, Yewseok Suh, B. Jack, Longley. Hasan Mukhtar Vijayasaradhi Setaluri Department of Dermatology, University of Wisconsin, Madison, WI 53706, USA E-mail addresses: [email protected] (H. Mukhtar), [email protected] (V. Setaluri).