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.Furthermore, ANGPTL2 increased its own expression in a feedback loop by activating the spleen tyrosine kinase-nuclear factor of activated T cells (Syk-NFAT) pathway.
Affiliation: Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.Show MeSH
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Mentions: We next carried out ANGPTL2 immunostaining using tissues from 92 CRC patients with unresectable tumors in order to correlate ANGPTL2 expression with the ORR to chemotherapy (Fig. 6, Table S2). Patients were placed into high- and low-ANGPTL2 groups: the high group showed ≥50% of ANGPTL2-positive tumor cells and the low showed <50% (Fig. 6a). The percentage of patients who showed a response to chemotherapy was significantly lower in the high-ANGPTL2 than the low-ANGPTL2 group (Fig. 6b, P < 0.05), although progression-free survival and overall survival did not differ significantly between groups (data not shown). This analysis suggests that high ANGPTL2 expression in CRC cells is associated with chemoresistance.
Affiliation: Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.