TAZ responds to fluid shear stress to regulate the cell cycle

Cell Cycle. 2018;17(2):147-153. doi: 10.1080/15384101.2017.1404209. Epub 2018 Jan 18.

Abstract

Physical forces associated with tumor growth and drainage alter cancer cell invasiveness and metastatic potential. We previously showed that fluid frictional force, or shear stress, typical of lymphatic flow induces YAP1/TAZ activation in prostate cancer cells to promote motility dependent upon YAP1 but not TAZ. Here, we show that shear stress elevates TAZ protein levels and promotes TAZ nuclear localization. Increased TAZ activity drives increased DNA synthesis and induces AMOTL2, ANKRD1, and CTGF gene transcription independently of YAP1. Ectopic expression of constitutively activated TAZ increases expression of these TAZ target genes and promotes cell proliferation of prostate cancer cells. Conversely, silencing of TAZ results in reduced proliferation. Together, our data show that force-induced TAZ regulates signaling that dictates cell division, and suggest that TAZ may govern cellular proliferation of cancer cells traveling through the lymphatics in response to biophysical cues.

Keywords: Cancer cells; Signal transduction; TAZ; Transcription factors; YAP1; biomechanical force; lymphatics; mechanotransduction; prostate cancer; shear stress.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Cell Cycle*
  • Cell Line, Tumor
  • Cell Proliferation
  • DNA, Neoplasm / biosynthesis
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Lymphatic System / physiology
  • Male
  • Mechanotransduction, Cellular*
  • Phosphoproteins / metabolism
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / physiopathology
  • Stress, Physiological
  • Trans-Activators
  • Transcription Factors

Substances

  • Adaptor Proteins, Signal Transducing
  • DNA, Neoplasm
  • Intracellular Signaling Peptides and Proteins
  • Phosphoproteins
  • Trans-Activators
  • Transcription Factors
  • WWTR1 protein, human
  • YAP1 (Yes-associated) protein, human