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pi3k/akt anti-apoptotic pathway simpson-golabi-behmel overgrowth syndrome month download article/chapter simpson-golabi-behmel syndrome wnt/pcp signaling pathway préstamo bid 1728/oc-ar mammary tumor cells anti-cancer drug development stimulates p53-dependent apoptosis real-time rt-pcr transcription factor nf-kappab oci-5/rat glypican-3 binds p38mapk signaling pathways cell line-specific manner p38mapk stress-activated breast cancer progression human breast cancer akt pathway full article pdf oridonin-induced apoptosis p38 protein kinases privacy choices/manage cookies related subjects glypican-3 regulates migration anti-apoptotic molecules breast cancer canonical pathway oncology “angel cell-specific manner heparan sulfate proteoglycans transcription factor nfat song hh lm3 cells protein-dye binding wnt signaling modulation scope submit manuscript division abnormally delayed hughes-benzie rm vousden kh glypican-3 induces alterations cell division pattering signaling network involved conditions privacy policy stigliano contributed equally european economic area fibroblast growth factor-2 article log accepting optional cookies 04 september 2023 1007/s10549-023-07120

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         description:Glypican-3 (GPC3) is a proteoglycan involved in proliferation and cell survival. Several reports demonstrated that GPC3 is downregulated in some tumors, such as breast cancer. Previously, we determined that GPC3 reexpression in the murine mammary adenocarcinoma LM3 cells induced an impairment of their invasive and metastatic capacities, associated with a decrease of their motility and an increase of their cell death. We demonstrated that GPC3 inhibits canonical Wnt signaling, as well as it activates non canonical pathway. Now, we identified signaling pathways responsible for the pro-apoptotic role of GPC3 in LM3 cells. We found for the first time that GPC3 inhibits the PI3K/Akt anti-apoptotic pathway while it stimulates the p38MAPK stress-activated one. We report a concomitant modulation of CDK inhibitors as well as of pro- and anti-apoptotic molecules. Our results provide new clues regarding the mechanism involved in the modulation induced by GPC3 of mammary tumor cell growth and survival.
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      description:Glypican-3 (GPC3) is a proteoglycan involved in proliferation and cell survival. Several reports demonstrated that GPC3 is downregulated in some tumors, such as breast cancer. Previously, we determined that GPC3 reexpression in the murine mammary adenocarcinoma LM3 cells induced an impairment of their invasive and metastatic capacities, associated with a decrease of their motility and an increase of their cell death. We demonstrated that GPC3 inhibits canonical Wnt signaling, as well as it activates non canonical pathway. Now, we identified signaling pathways responsible for the pro-apoptotic role of GPC3 in LM3 cells. We found for the first time that GPC3 inhibits the PI3K/Akt anti-apoptotic pathway while it stimulates the p38MAPK stress-activated one. We report a concomitant modulation of CDK inhibitors as well as of pro- and anti-apoptotic molecules. Our results provide new clues regarding the mechanism involved in the modulation induced by GPC3 of mammary tumor cell growth and survival.
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