- Email: [email protected]
AKT-1 for Survival
TERT activation provides a strong strategy for generating targeted therapeutics at TERT in these lethal human cancers.
require Fak, whereas HCT116 do not require PI3-K/Akt-1. 3- As in the case of differentiated enterocytes, HCT116, T84 and HT29 cells require Src and MEK/Erk for their survival, whereas undifferentiated/crypt enterocytes require Src only. 4- In contrast to both undifferentiated and differentiated enterocytes, HT29, T84 and HCT116 exhibit a sustained activation of Src and MEK/Erk while kept under anoikis-inducing conditions. 5- The inhibition of EGFR activity abrogated anoikis resistance in HCT116, HT29 and T84 cells, by causing a drop of SrcMEK/Erk activation. Conclusions: These data indicate that an illicit activation of EGFR in colon cancer cells through high secretion of EGF/TGFα under anoikis conditions will result in a sustained activation of the Src-MEK/Erk pathway, thus overriding a Fak, PI3-K/Akt-1 dependence for survival and consequently conferring high anoikis resistance. (supported by the CRS & FRSQ)
AGA Abstracts
W1965 Uncoupling Protein-2 Alters the p53 Response and the Bioenergetics of Colon Cancer Cells Zoltan Derdak, Nicholas M. Mark, Tamako A. Garcia, Guido Beldi, Simon C. Robson, Jack R. Wands, Gyorgy Baffy Background and Aims. Cancer cells acquire chemoresistance by selection pressure in response to an unfavorable microenvironment. This process is modulated by oxidative stress that primarily originates from mitochondria. Our study aimed to determine if this critical adaptive response in cancer cells is linked to uncoupling protein-2 (UCP2), a recently established regulator of mitochondrial reactive oxygen species (ROS) production with enhanced expression in human colon cancer. Methods. Full-length human UCP2 was overexpressed in HCT116 human colon cancer cells and the effect of various chemotherapeutic agents was analyzed In Vitro and In Vivo. Impact of UCP2 on intracellular ROS levels, apoptosis rates, and bioenergetics of cultured HCT116 cells was assessed in response to various chemotherapeutics such as camptothecin (CPT), etoposide, cisplatin, and doxorubicin. To monitor the effect of UCP2 on tumor growth In Vivo, NCr nu/nu mice with subcutaneous xenografts of UCP2 overexpressing HCT116 cells were treated with irinotecan (CPT-11). Results. UCP2 overexpression caused lower ROS levels and apoptosis rates in HCT116 cells treated with chemotherapeutics. The protective effect of UCP2 was absent in p53-/- HCT116 cells, while CPT-induced N-terminal phosphorylation of p53 in UCP2 overexpressing HCT116 cells was diminished at the Ser15, Ser33, and Ser46 residues. UCP2 overexpressing HCT116 cells produce progressively more lactate and show increased growth inhibition in response to the glycolytic inhibitor 2-deoxyglucose, consistent with increasing dependence on glycolytic ATP production. Finally, growth inhibitory effect of CPT-11 was diminished in mice receiving xenografts of UCP2-overexpressing cells when compared to empty vector controls. Conclusions. UCP2 has a protective effect in colon cancer cells treated with chemotherapeutics and this response involves modulation of the p53 response. Moreover, UCP2 overexpression promotes the glycolytic phenotype (Warburg effect) associated with chemoresistance in cancer cells. These findings suggest that UCP2 may become a novel target of our efforts to improve the treatment of advanced colon cancer. This work was supported by NIH grants DK-61890 and RR-17695.
W1968 Human Gastric Cancer-Associated Fibroblast-Like Cells Are Derived from the Bone Marrow Daniel L. Worthley, Andrew Ruszkiewicz, Ruth Davies, Sarah Moore, Simon Durrant, Robyn Western, Ian Nivison-Smith, Charles G. Mullighan, Peter Browett, Bik To, Graeme P. Young, Peter G. Bardy, Michael Michael BACKGROUND: A mouse model of gastric cancer suggested that bone-marrow derived cells (BMDCs) contribute to both the neoplastic glands as well as to the peritumoral stroma. Carcinoma-associated fibroblasts play a critical role in carcinogenesis. The origin of carcinoma-associated fibroblasts is uncertain. Theories include mesenchymal transition from adjacent epithelium, proliferation of resident cells and recruitment of fibrocyte-precursors from the bone marrow. METHODS: To address these questions in humans, we analyzed secondary cancers following gender discordant allogeneic stem cell transplantation (allo-SCTs). From the paraffin blocks of such cancers, BMDCs can be identified by the presence or absence of the Y-chromosome. 12,536 transplants from the Australasian Bone Marrow Transplant Recipient Registry were reviewed, and several Asian allo-SCT centres were contacted. 17 cancer cases satisfied our criteria; female recipients of male grafts that developed secondary, solid organ cancers, or any gender discordant transplant that developed secondary gastric cancer. Light microscopy, fluorescence (FISH) and chromagenic (CISH) in situ hybridization for the sex chromosomes was performed on all cases. RESULTS: The cancers included skin cancers, cervical intraepithelial neoplasia, melanomas, and two gastric cancer cases. Y chromosomes were found in all nucleated haematopoietic cells, with a dense inflammatory infiltrate invading several of the tumours, but no Y chromosomes were found in any of the neoplastic cells. In all of the cancer cells only the recipients' sex chromosomes were evident. In the desmoplastic reaction that surrounded the invading gastric cancer, however, many spindle-shaped, fibroblast-like cells were identified. These cells were shown to contain Ychromosomes on CISH, confirming bone marrow origin. Only fibroblast-like cells that were adjacent to the tumor contained Y-chromosomes, suggesting that they were recruited by the cancer. The fibroblast phenotype of these cells is being confirmed by immunohistochemistry (smooth muscle actin, collagen, FSP-1, CD45 and CD31). CONCLUSIONS: Donor-derived BMDCs did not directly contribute to the neoplastic tissue. This finding is still consistent with the BMD hypothesis of gastric cancer as the BMDCs were shown to engraft at the chronic gastritis stage, which would have predated allo-SCT in our patients. If the fibroblast phenotype is confirmed, this study will, for the first time in humans, confirm that carcinomaassociated fibroblasts are derived from the bone marrow.
W1966 Hom-1 Inhibits Tumor Growth in Both p53 Sufficient and Deficient Colon Cancer Cells Hong (Jenny) Gao, Bin Wu, Roger Giese, John R. Saltzman, Zhenglun (Jerry) Zhu Wnt/b-catenin signaling is an essential cell fate determination pathway of early embryogenesis. Gain of function mutations of the Wnt/b-catenin pathway has been implicated in the pathogenesis of a variety of GI malignancies, such as colorectal cancer and hepatocellular carcinoma. To identify potential method of regulating Wnt/b-catenin signaling, we have utilized the vertebrate Xenopus laevis model system to model the signal and transcriptional network that control cell fate determination and identified Xom as a novel factor that modulate Wnt/ b-catenin signaling. To further explore the significance of the finings, we have used methods of comparative genomics, and identified a human homologue of Xom, Hom-1. To determine the potential role of Hom-1 in tumorigenesis, we examined the effects of Hom-1 expression on colon cancer cell proliferation, using the HCT116 cells. Using cell proliferation assay and cell metabolic assays, we found that Hom-1 expression inhibits colon cancer cell growth in tissue cultures. To further explore the potential growth inhibitory effects of Hom-1 on cancer cell growth, we expressed the Hom-1 in HCT116 cells and examined its effects oh tumor formation in nude mice. We found that the tumor volume in Hom-1 expression tumor is 60% of the tumor volume of control tumors, which is consistent to the level of Hom-1 expression. To explore the molecular mechanism underlying the Hom-1 effects on cancer cell growth, we found that Hom-1 expression induces the activation of caspase-3, and leads to the cleavage of its substrates such as PARP. In addition, we found that the Hom-1 exerts its effects on tumor cell growth in both p53 sufficient and in deficient cells. In summery, through developmental modeling and methods of comparative genomics, we have identified a human homologue of Xom, our data suggest a potential tumor suppressor role of Hom-1 in both p53 sufficient and deficient cancer cells.
W1969 Translation Control During Mitotic Catastrophe: Mcl-1 Is a Novel Target for RNA Binding Protein CUGBP2 Dharmalingam Subramaniam, Satish Ramalingam, Gopalan Natarajan, Ilangovan Ramachandran, Randal May, Lurdes Queimado, Courtney W. Houchen, Shrikant Anant Introduction: Overexpression of CUGBP2 protein induces intestinal epithelial cells to undergo apoptosis. We have shown that CUGBP2 binds to AU-rich sequences in the 3' untranslated region (3'UTR) of COX-2 mRNA and stabilizes the mRNA but inhibits its translation. Myeloid cell leukemia-1 (Mcl-1) is an anti-apoptotic Bcl-2 family protein that interferes with mitochondrial activation to inhibit apoptosis. Therefore, the aim of this study was to determine the effect of CUGBP2 on Mcl-1 expression in intestinal epithelial cells. Methods: We developed a HCUG2 cell line by stably expressing CUGBP2 in the HCT 116 colon cancer cells. Cell proliferation and apoptosis were assessed by hexosaminidase and caspase 3/7 assays, respectively. Cell cycle progression was done by flow cytometry analysis. The full length 2.8 kb Mcl-1 3' UTR was cloned downstream of the luciferase gene in pGL3Control plasmid. Luciferase activity was determined in cell lysates using the Luciferase Assay System (Promega). CUGBP2 binding to Mcl-1 3'UTR was determined by electrophoretic mobility shift assay using a 32P-labeled Mcl-1 3'UTR. Binding to Mcl-1 mRNA in the cells was determined by a coupled immunoprecipitation-RT-PCR assay. mRNA stability was measured by Real Time PCR. Results: Overexpression of CUGBP2 in HCUG2 cells reduced cell proliferation and induced apoptosis. In addition, the number of cells in the G2/M phase was significantly higher. Western blot analyses demonstrated that there was decreased Bcl2 and Mcl-1 protein expression while there was increased expression of Bax, cyclin B1 and Cdc2. In addition, immunocytochemistry demonstrated increased levels of cyclin B1 and Cdc2 in the nucleus of HCUG2 cells. These data suggest that CUGBP2 expression in HCUG2 cells induces the cells to undergo mitotic catastrophe. We next determined the mechanism of CUGBP2-mediated reduction in Mcl-1 expression. While HCUG2 cells had lower Mcl-1 protein expression than HCT-116 cells, Mcl-1 mRNA levels were increased, suggesting translation inhibition. RNA binding studies demonstrated that CUGBP2 binds to Mcl-1 3'UTR both In Vitro and in HCUG2 cells. Furthermore CUGBP2 increased the stability of both endogenous Mcl-1 and luciferase mRNA containing the Mcl-1 3'UTR, the half-life increasing from 30 min in HCT-116 cells to 3 h in HCUG2 cells. However, luciferase protein expression from the luciferase-Mcl-1 3'UTR mRNA was suppressed. Conclusion: Taken together, these data demonstrate that CUGBP2 inhibits Mcl-1 expression by inhibiting Mcl-1 mRNA translation, resulting in driving the cells to mitotic catastrophe. These data demonstrate that Mcl-1 is a novel target for RNA binding protein CUGBP2.
W1967 Colon Cancer Cells and Anoikis Resistance: EGFR-Dependent Sustained Activation of the SRC-MEK/ERK Pathway Can Override Dependance On FAK, PI3-K/AKT-1 for Survival. Pierre H. Vachon Background/Aims: Anoikis resistance is a landmark of invasive cancer cells. In the present study, we investigated the cell surviving properties of colon cancer cells with regards to anoikis resistance. Methods: Colon cancer cells HCT116 and HT29, which do not differentiate, and T84, which polarize but not differentiate, were compared to undifferentiated (-2 PC) and differentiated (30 PC) enterocyte-like Caco-2/15 cells, as well as to normal human crypt cells (HIEC). HCT116, HT29 and T84 cells are known for their high EGF/TGFα autocrine secretory activities, in sharp contrast to Caco-2/15 and HIEC cells. EGFR, Fak, Src, the MEK/Erk and/or PI3-K/Akt-1 pathways were inhibited either pharmacologically or by overexpression of dominant negative mutants. Cells were also kept in suspension on poly-HEMA for 0-24 hrs. Anoikis was evaluated by ISEL and/or DNA laddering. Activation parameters of Fak, Src, Erk-1/Erk-2 and Akt-1 were analyzed. All experiments were performed under serum-free conditions. Results: 1- Differentiated enterocytes are more susceptible to anoikis than undifferentiated/crypt ones. However, HCT116, HT29 and T84 cells displayed significantly greater anoikis resistance overall. 2- Differentiated and undifferentiated enterocytes require Fak and the PI3-K/Akt-1 pathway for their survival. However, T84 cells do not
AGA Abstracts
A-744
require Fak, whereas HCT116 do not require PI3-K/Akt-1. 3- As in the case of differentiated enterocytes, HCT116, T84 and HT29 cells require Src and MEK/Erk for their survival, whereas undifferentiated/crypt enterocytes require Src only. 4- In contrast to both undifferentiated and differentiated enterocytes, HT29, T84 and HCT116 exhibit a sustained activation of Src and MEK/Erk while kept under anoikis-inducing conditions. 5- The inhibition of EGFR activity abrogated anoikis resistance in HCT116, HT29 and T84 cells, by causing a drop of SrcMEK/Erk activation. Conclusions: These data indicate that an illicit activation of EGFR in colon cancer cells through high secretion of EGF/TGFα under anoikis conditions will result in a sustained activation of the Src-MEK/Erk pathway, thus overriding a Fak, PI3-K/Akt-1 dependence for survival and consequently conferring high anoikis resistance. (supported by the CRS & FRSQ)
AGA Abstracts
W1965 Uncoupling Protein-2 Alters the p53 Response and the Bioenergetics of Colon Cancer Cells Zoltan Derdak, Nicholas M. Mark, Tamako A. Garcia, Guido Beldi, Simon C. Robson, Jack R. Wands, Gyorgy Baffy Background and Aims. Cancer cells acquire chemoresistance by selection pressure in response to an unfavorable microenvironment. This process is modulated by oxidative stress that primarily originates from mitochondria. Our study aimed to determine if this critical adaptive response in cancer cells is linked to uncoupling protein-2 (UCP2), a recently established regulator of mitochondrial reactive oxygen species (ROS) production with enhanced expression in human colon cancer. Methods. Full-length human UCP2 was overexpressed in HCT116 human colon cancer cells and the effect of various chemotherapeutic agents was analyzed In Vitro and In Vivo. Impact of UCP2 on intracellular ROS levels, apoptosis rates, and bioenergetics of cultured HCT116 cells was assessed in response to various chemotherapeutics such as camptothecin (CPT), etoposide, cisplatin, and doxorubicin. To monitor the effect of UCP2 on tumor growth In Vivo, NCr nu/nu mice with subcutaneous xenografts of UCP2 overexpressing HCT116 cells were treated with irinotecan (CPT-11). Results. UCP2 overexpression caused lower ROS levels and apoptosis rates in HCT116 cells treated with chemotherapeutics. The protective effect of UCP2 was absent in p53-/- HCT116 cells, while CPT-induced N-terminal phosphorylation of p53 in UCP2 overexpressing HCT116 cells was diminished at the Ser15, Ser33, and Ser46 residues. UCP2 overexpressing HCT116 cells produce progressively more lactate and show increased growth inhibition in response to the glycolytic inhibitor 2-deoxyglucose, consistent with increasing dependence on glycolytic ATP production. Finally, growth inhibitory effect of CPT-11 was diminished in mice receiving xenografts of UCP2-overexpressing cells when compared to empty vector controls. Conclusions. UCP2 has a protective effect in colon cancer cells treated with chemotherapeutics and this response involves modulation of the p53 response. Moreover, UCP2 overexpression promotes the glycolytic phenotype (Warburg effect) associated with chemoresistance in cancer cells. These findings suggest that UCP2 may become a novel target of our efforts to improve the treatment of advanced colon cancer. This work was supported by NIH grants DK-61890 and RR-17695.
W1968 Human Gastric Cancer-Associated Fibroblast-Like Cells Are Derived from the Bone Marrow Daniel L. Worthley, Andrew Ruszkiewicz, Ruth Davies, Sarah Moore, Simon Durrant, Robyn Western, Ian Nivison-Smith, Charles G. Mullighan, Peter Browett, Bik To, Graeme P. Young, Peter G. Bardy, Michael Michael BACKGROUND: A mouse model of gastric cancer suggested that bone-marrow derived cells (BMDCs) contribute to both the neoplastic glands as well as to the peritumoral stroma. Carcinoma-associated fibroblasts play a critical role in carcinogenesis. The origin of carcinoma-associated fibroblasts is uncertain. Theories include mesenchymal transition from adjacent epithelium, proliferation of resident cells and recruitment of fibrocyte-precursors from the bone marrow. METHODS: To address these questions in humans, we analyzed secondary cancers following gender discordant allogeneic stem cell transplantation (allo-SCTs). From the paraffin blocks of such cancers, BMDCs can be identified by the presence or absence of the Y-chromosome. 12,536 transplants from the Australasian Bone Marrow Transplant Recipient Registry were reviewed, and several Asian allo-SCT centres were contacted. 17 cancer cases satisfied our criteria; female recipients of male grafts that developed secondary, solid organ cancers, or any gender discordant transplant that developed secondary gastric cancer. Light microscopy, fluorescence (FISH) and chromagenic (CISH) in situ hybridization for the sex chromosomes was performed on all cases. RESULTS: The cancers included skin cancers, cervical intraepithelial neoplasia, melanomas, and two gastric cancer cases. Y chromosomes were found in all nucleated haematopoietic cells, with a dense inflammatory infiltrate invading several of the tumours, but no Y chromosomes were found in any of the neoplastic cells. In all of the cancer cells only the recipients' sex chromosomes were evident. In the desmoplastic reaction that surrounded the invading gastric cancer, however, many spindle-shaped, fibroblast-like cells were identified. These cells were shown to contain Ychromosomes on CISH, confirming bone marrow origin. Only fibroblast-like cells that were adjacent to the tumor contained Y-chromosomes, suggesting that they were recruited by the cancer. The fibroblast phenotype of these cells is being confirmed by immunohistochemistry (smooth muscle actin, collagen, FSP-1, CD45 and CD31). CONCLUSIONS: Donor-derived BMDCs did not directly contribute to the neoplastic tissue. This finding is still consistent with the BMD hypothesis of gastric cancer as the BMDCs were shown to engraft at the chronic gastritis stage, which would have predated allo-SCT in our patients. If the fibroblast phenotype is confirmed, this study will, for the first time in humans, confirm that carcinomaassociated fibroblasts are derived from the bone marrow.
W1966 Hom-1 Inhibits Tumor Growth in Both p53 Sufficient and Deficient Colon Cancer Cells Hong (Jenny) Gao, Bin Wu, Roger Giese, John R. Saltzman, Zhenglun (Jerry) Zhu Wnt/b-catenin signaling is an essential cell fate determination pathway of early embryogenesis. Gain of function mutations of the Wnt/b-catenin pathway has been implicated in the pathogenesis of a variety of GI malignancies, such as colorectal cancer and hepatocellular carcinoma. To identify potential method of regulating Wnt/b-catenin signaling, we have utilized the vertebrate Xenopus laevis model system to model the signal and transcriptional network that control cell fate determination and identified Xom as a novel factor that modulate Wnt/ b-catenin signaling. To further explore the significance of the finings, we have used methods of comparative genomics, and identified a human homologue of Xom, Hom-1. To determine the potential role of Hom-1 in tumorigenesis, we examined the effects of Hom-1 expression on colon cancer cell proliferation, using the HCT116 cells. Using cell proliferation assay and cell metabolic assays, we found that Hom-1 expression inhibits colon cancer cell growth in tissue cultures. To further explore the potential growth inhibitory effects of Hom-1 on cancer cell growth, we expressed the Hom-1 in HCT116 cells and examined its effects oh tumor formation in nude mice. We found that the tumor volume in Hom-1 expression tumor is 60% of the tumor volume of control tumors, which is consistent to the level of Hom-1 expression. To explore the molecular mechanism underlying the Hom-1 effects on cancer cell growth, we found that Hom-1 expression induces the activation of caspase-3, and leads to the cleavage of its substrates such as PARP. In addition, we found that the Hom-1 exerts its effects on tumor cell growth in both p53 sufficient and in deficient cells. In summery, through developmental modeling and methods of comparative genomics, we have identified a human homologue of Xom, our data suggest a potential tumor suppressor role of Hom-1 in both p53 sufficient and deficient cancer cells.
W1969 Translation Control During Mitotic Catastrophe: Mcl-1 Is a Novel Target for RNA Binding Protein CUGBP2 Dharmalingam Subramaniam, Satish Ramalingam, Gopalan Natarajan, Ilangovan Ramachandran, Randal May, Lurdes Queimado, Courtney W. Houchen, Shrikant Anant Introduction: Overexpression of CUGBP2 protein induces intestinal epithelial cells to undergo apoptosis. We have shown that CUGBP2 binds to AU-rich sequences in the 3' untranslated region (3'UTR) of COX-2 mRNA and stabilizes the mRNA but inhibits its translation. Myeloid cell leukemia-1 (Mcl-1) is an anti-apoptotic Bcl-2 family protein that interferes with mitochondrial activation to inhibit apoptosis. Therefore, the aim of this study was to determine the effect of CUGBP2 on Mcl-1 expression in intestinal epithelial cells. Methods: We developed a HCUG2 cell line by stably expressing CUGBP2 in the HCT 116 colon cancer cells. Cell proliferation and apoptosis were assessed by hexosaminidase and caspase 3/7 assays, respectively. Cell cycle progression was done by flow cytometry analysis. The full length 2.8 kb Mcl-1 3' UTR was cloned downstream of the luciferase gene in pGL3Control plasmid. Luciferase activity was determined in cell lysates using the Luciferase Assay System (Promega). CUGBP2 binding to Mcl-1 3'UTR was determined by electrophoretic mobility shift assay using a 32P-labeled Mcl-1 3'UTR. Binding to Mcl-1 mRNA in the cells was determined by a coupled immunoprecipitation-RT-PCR assay. mRNA stability was measured by Real Time PCR. Results: Overexpression of CUGBP2 in HCUG2 cells reduced cell proliferation and induced apoptosis. In addition, the number of cells in the G2/M phase was significantly higher. Western blot analyses demonstrated that there was decreased Bcl2 and Mcl-1 protein expression while there was increased expression of Bax, cyclin B1 and Cdc2. In addition, immunocytochemistry demonstrated increased levels of cyclin B1 and Cdc2 in the nucleus of HCUG2 cells. These data suggest that CUGBP2 expression in HCUG2 cells induces the cells to undergo mitotic catastrophe. We next determined the mechanism of CUGBP2-mediated reduction in Mcl-1 expression. While HCUG2 cells had lower Mcl-1 protein expression than HCT-116 cells, Mcl-1 mRNA levels were increased, suggesting translation inhibition. RNA binding studies demonstrated that CUGBP2 binds to Mcl-1 3'UTR both In Vitro and in HCUG2 cells. Furthermore CUGBP2 increased the stability of both endogenous Mcl-1 and luciferase mRNA containing the Mcl-1 3'UTR, the half-life increasing from 30 min in HCT-116 cells to 3 h in HCUG2 cells. However, luciferase protein expression from the luciferase-Mcl-1 3'UTR mRNA was suppressed. Conclusion: Taken together, these data demonstrate that CUGBP2 inhibits Mcl-1 expression by inhibiting Mcl-1 mRNA translation, resulting in driving the cells to mitotic catastrophe. These data demonstrate that Mcl-1 is a novel target for RNA binding protein CUGBP2.
W1967 Colon Cancer Cells and Anoikis Resistance: EGFR-Dependent Sustained Activation of the SRC-MEK/ERK Pathway Can Override Dependance On FAK, PI3-K/AKT-1 for Survival. Pierre H. Vachon Background/Aims: Anoikis resistance is a landmark of invasive cancer cells. In the present study, we investigated the cell surviving properties of colon cancer cells with regards to anoikis resistance. Methods: Colon cancer cells HCT116 and HT29, which do not differentiate, and T84, which polarize but not differentiate, were compared to undifferentiated (-2 PC) and differentiated (30 PC) enterocyte-like Caco-2/15 cells, as well as to normal human crypt cells (HIEC). HCT116, HT29 and T84 cells are known for their high EGF/TGFα autocrine secretory activities, in sharp contrast to Caco-2/15 and HIEC cells. EGFR, Fak, Src, the MEK/Erk and/or PI3-K/Akt-1 pathways were inhibited either pharmacologically or by overexpression of dominant negative mutants. Cells were also kept in suspension on poly-HEMA for 0-24 hrs. Anoikis was evaluated by ISEL and/or DNA laddering. Activation parameters of Fak, Src, Erk-1/Erk-2 and Akt-1 were analyzed. All experiments were performed under serum-free conditions. Results: 1- Differentiated enterocytes are more susceptible to anoikis than undifferentiated/crypt ones. However, HCT116, HT29 and T84 cells displayed significantly greater anoikis resistance overall. 2- Differentiated and undifferentiated enterocytes require Fak and the PI3-K/Akt-1 pathway for their survival. However, T84 cells do not
AGA Abstracts
A-744