TSPAN12 is a critical factor for cancer-fibroblast cell contact-mediated cancer invasion
Abstract
Cancer-associated fibroblasts (CAFs) are abundant and promote cancer proliferation, invasion, and metastasis. Mutations in the p53 gene and decreased p53 expression are often detected in CAFs, and a dysfunction in p53 in CAFs contributes to cancer progression. However, how host-derived p53 influences cancer cells remains unclear. We herein established coculture systems to monitor enhancements in invasiveness and proliferation elicited by p53-depleted fibroblasts and demonstrated that tetraspanin 12 (TSPAN12), identified as a p53-regulated gene, was required for these processes through the contact of cancer cells with stromal fibroblasts and β-catenin-mediated CXC chemokine ligand 6 (CXCL6) secretion. These results suggest that antibodies against TSPAN12 and CXCL6 may be effective therapeutic agents for cancer.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- December 2014
- DOI:
- 10.1073/pnas.1412062112
- Bibcode:
- 2014PNAS..11118691O