| First Author | Zhang S | Year | 2018 |
| Journal | Cancer Lett | Volume | 419 |
| Pages | 116-127 | PubMed ID | 29355659 |
| Mgi Jnum | J:257818 | Mgi Id | MGI:6119074 |
| Doi | 10.1016/j.canlet.2018.01.045 | Citation | Zhang S, et al. (2018) Sorting nexin 10 acts as a tumor suppressor in tumorigenesis and progression of colorectal cancer through regulating chaperone mediated autophagy degradation of p21(Cip1/WAF1). Cancer Lett 419:116-127 |
| abstractText | Chaperone-mediated autophagy (CMA) characterized by the selective degradation of target proteins has been linked with tumorigenesis in recent years. Here, we explored the function of sorting nexin 10 (SNX10), a protein involved in maintaining endosome/lysosome homeostasis, in mediating CMA activity and its impact on the progression of mouse inflammation-driven colorectal cancer. Our results revealed that SNX10 deficiency increased the activation of CMA by preventing the degradation of lysosomal LAMP-2A. In SNX10 KO cells, we disclosed that p21(Cip1/WAF1), a master effector in various tumor suppressor pathways, is a substrate of CMA, and decrease of p21(Cip1/WAF1) caused by SNX10-mediated CMA activation contributes to HCT116cell proliferation and survival. Moreover, we found that SNX10 KO promoted tumorigenesis in the mouse colorectum which could be restored by SNX10 over-expression. Furthermore, SNX10 was remarkably down-regulated in human CRC tissues which showed the increased activity of CMA and decreased expression of p21(Cip1/WAF1). These findings suggest that SNX10 acts as a tumor suppressor in the mouse colorectum and drives inflammation-associated colorectal cancer by a chaperone-mediated autophagy mechanism. |
