Angiopoietin-like protein 2 renders colorectal cancer cells resistant to chemotherapy by activating spleen tyrosine kinase-phosphoinositide 3-kinase-dependent anti-apoptotic signaling.
Bottom Line: Apoptosis induced by antineoplastic drug treatment was significantly decreased in SW480/ANGPTL2 compared to control cells.Expression of anti-apoptotic BCL-2 family genes was upregulated in SW480/ANGPTL2 compared to SW480/Ctrl cells.To assess signaling downstream of ANGPTL2 underlying this effect, we carried out RNA sequencing analysis of SW480/ANGPTL2 and SW480/Ctrl cells.
Affiliation: Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.Show MeSH
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Mentions: In summary, we have shown that ANGPTL2 promotes CRC cell survival after antineoplastic drug treatment by regulating anti-apoptotic BCL-2 family genes through Syk–PI3K signaling. Furthermore, ANGPTL2 positively autoregulated its own expression through the Syk–NFAT pathway (Fig. 7). We also showed that CRC cells expressing relatively high levels of ANGPTL2 may develop resistance to chemotherapy. These findings possibly suggest novel approaches to counteracting chemoresistance based on attenuating ANGPTL2 signaling in tumor cells.
Affiliation: Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.