Wnt5a in cancer-associated fibroblasts promotes colorectal cancer progression

Tomoaki Hirashima, Hideaki Karasawa, Takashi Aizawa, Takashi Suzuki, Akihiro Yamamura, Hideyuki Suzuki, Taiki Kajiwara, Hiroaki Musha, Ryo Funayama, Matsuyuki Shirota, Shinobu Ohnuma, Keiko Nakayama, Michiaki Unno

Research output: Contribution to journalArticlepeer-review

Abstract

Cancer-associated fibroblasts (CAFs) are a major component of the tumor microenvironment and have been shown to promote cancer aggressiveness. In our previous study, analysis of expression profiles obtained from paired CAFs and normal fibroblasts from colorectal cancer (CRC) tissue revealed that gene sets related to the Wnt signaling pathway were highly enriched in colorectal CAFs. Furthermore, among the components of the β-catenin-independent Wnt pathway, Wnt5a was highly expressed in CAFs. Since Wnt5a is considered to be a regulator of CRC progression in CAFs, we performed immunohistochemical analysis on Wnt5a in 171 patients who underwent surgery for CRC. Positive staining for Wnt5a was often found in cancer stroma, particularly in fibromatous areas, although the immunoreactivity for Wnt5a was weak in cancer cells. Wnt5a status in CAFs was significantly associated with tumor size, depth of invasion, lymphatic and vascular invasion, lymph node metastasis, TNM stage, and recurrence. Subsequent in vitro analyses using human recombinant Wnt5a protein revealed that cancer cell proliferation and migration were significantly increased by stimulation with Wnt5a. Our findings suggest that Wnt5a-derived CAFs play a crucial role in CRC progression and have potential as a target of anti-cancer therapies.

Original languageEnglish
Pages (from-to)37-42
Number of pages6
JournalBiochemical and biophysical research communications
Volume568
DOIs
Publication statusPublished - 2021 Sep 3

Keywords

  • Cancer-associated fibroblast
  • Colorectal cancer
  • Tumor microenvironment
  • Wnt5a

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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