Affiliation:
1. University of Michigan Health System
Abstract
Abstract
Bladder cancer is a common malignancy whose lethality is determined by invasive potential. We have previously shown that TRIM29, also known as ATDC, is transcriptionally regulated by TP63 in basal bladder cancers where it promotes invasive progression and metastasis, but the molecular events which promote invasion and metastasis downstream of TRIM29 remained poorly understood. Here we identify stimulation of bladder cancer migration as the specific role of TRIM29 during invasion. We show that TRIM29 physically interacts with K14 + intermediate filaments which in turn regulates focal adhesion stability. Further, we find that both K14 and the focal adhesion protein, ZYX are required for bladder cancer migration and invasion. Taken together, these results establish a role for TRIM29 in the regulation of cytoskeleton and focal adhesions during invasion and identify a pathway with therapeutic potential.
Publisher
Research Square Platform LLC
Reference40 articles.
1. Islami F, Ward EM, Sung H, Cronin KA, Tangka FKL, Sherman RL et al. Annual Report to the Nation on the Status of Cancer, Part 1: National Cancer Statistics. J Natl Cancer Inst 2021.
2. ATDC/TRIM29 Drives Invasive Bladder Cancer Formation through miRNA-Mediated and Epigenetic Mechanisms;Palmbos PL;Cancer Res,2015
3. ATDC mediates a TP63-regulated basal cancer invasive program;Palmbos PL;Oncogene,2019
4. Collective invasion in breast cancer requires a conserved basal epithelial program;Cheung KJ;Cell,2013
5. Intermediate filaments and the regulation of focal adhesion;Leube RE;Curr Opin Cell Biol,2015