High-Temperature Requirement A1 (Htra1) - A Novel Regulator of Canonical Wnt Signaling

Sci Rep. 2017 Dec 21;7(1):17995. doi: 10.1038/s41598-017-18203-2.


Different cancer types as well as many other diseases are caused by aberrant activation of the canonical Wnt signal transduction pathway, and it is especially implicated in the development and progression of colorectal cancer (CRC). The main effector protein of the canonical Wnt signaling cascade is β-catenin, which binds to the T- cell factor/lymphoid enhancer factor (TCF/LEF) and triggers the activation of Wnt target genes. Here, we identify the serine protease High-Temperature Requirement A1 (HTRA1) as a novel component of the canonical Wnt pathway. We show that the HTRA1 protein inhibits the Wnt/β-catenin signaling, in both paracrine and autocrine manners, and affects the expression of several Wnt target genes. Moreover, HTRA1 forms a complex with β-catenin and reduces the proliferation rates of cells. Taken together, our findings indicate that HTRA1 functions as a novel suppressor of the canonical Wnt signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Line
  • Fluorescent Antibody Technique
  • HEK293 Cells
  • High-Temperature Requirement A Serine Peptidase 1 / physiology*
  • Humans
  • Immunoprecipitation
  • Real-Time Polymerase Chain Reaction
  • Wnt Signaling Pathway / physiology*


  • High-Temperature Requirement A Serine Peptidase 1
  • HtrA1 protein, human