| First Author | Seguin L | Year | 2017 |
| Journal | Cancer Discov | Volume | 7 |
| Issue | 12 | Pages | 1464-1479 |
| PubMed ID | 28893801 | Mgi Jnum | J:252287 |
| Mgi Id | MGI:6103439 | Doi | 10.1158/2159-8290.CD-17-0539 |
| Citation | Seguin L, et al. (2017) Galectin-3, a Druggable Vulnerability for KRAS-Addicted Cancers. Cancer Discov 7(12):1464-1479 |
| abstractText | Identifying the molecular basis for cancer cell dependence on oncogenes such as KRAS can provide new opportunities to target these addictions. Here, we identify a novel role for the carbohydrate-binding protein galectin-3 as a lynchpin for KRAS dependence. By directly binding to the cell surface receptor integrin alphavbeta3, galectin-3 gives rise to KRAS addiction by enabling multiple functions of KRAS in anchorage-independent cells, including formation of macropinosomes that facilitate nutrient uptake and ability to maintain redox balance. Disrupting alphavbeta3/galectin-3 binding with a clinically active drug prevents their association with mutant KRAS, thereby suppressing macropinocytosis while increasing reactive oxygen species to eradicate alphavbeta3-expressing KRAS-mutant lung and pancreatic cancer patient-derived xenografts and spontaneous tumors in mice. Our work reveals galectin-3 as a druggable target for KRAS-addicted lung and pancreas cancers, and indicates integrin alphavbeta3 as a biomarker to identify susceptible tumors.Significance: There is a significant unmet need for therapies targeting KRAS-mutant cancers. Here, we identify integrin alphavbeta3 as a biomarker to identify mutant KRAS-addicted tumors that are highly sensitive to inhibition of galectin-3, a glycoprotein that binds to integrin alphavbeta3 to promote KRAS-mediated activation of AKT. Cancer Discov; 7(12); 1464-79. (c)2017 AACR.This article is highlighted in the In This Issue feature, p. 1355. |
