Inhibition of protein tyrosine phosphatase receptor type F suppresses Wnt signaling in colorectal cancer

Tong Gan, Ashley T. Stevens, Xiaopeng Xiong, Yang An Wen, Trevor N. Farmer, Austin T. Li, Payton D. Stevens, Sanam Golshani, Heidi L. Weiss, B. Mark Evers, Tianyan Gao

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Wnt signaling dysregulation promotes tumorigenesis in colorectal cancer (CRC). We investigated the role of PTPRF, a receptor-type tyrosine phosphatase, in regulating Wnt signaling in CRC. Knockdown of PTPRF decreased cell proliferation in patient-derived primary colon cancer cells and established CRC cell lines. In addition, the rate of proliferation as well as colony formation ability were significantly decreased in tumor organoids grown in 3D, whereas the number of differentiated tumor organoids were markedly increased. Consistently, knockdown of PTPRF resulted in a decrease in the expression of genes associated with cancer stem cells downstream of Wnt/β-catenin signaling. Treating PTPRF knockdown cells with GSK3 inhibitor rescued the expression of Wnt target genes suggesting that PTPRF functions upstream of the β-catenin destruction complex. PTPRF was found to interact with LRP6 and silencing PTPRF largely decreased the activation of LRP6. Interestingly, this PTPRF-mediated activation of Wnt signaling was blocked in cells treated with clathrin endocytosis inhibitor. Furthermore, knockdown of PTPRF inhibited xenograft tumor growth in vivo and decreased the expression of Wnt target genes. Taken together, our studies identify a novel role of PTPRF as an oncogenic protein phosphatase in supporting the activation of Wnt signaling in CRC.

Original languageEnglish
Pages (from-to)6789-6801
Number of pages13
JournalOncogene
Volume39
Issue number44
DOIs
StatePublished - Oct 29 2020

Bibliographical note

Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature Limited.

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Fingerprint

Dive into the research topics of 'Inhibition of protein tyrosine phosphatase receptor type F suppresses Wnt signaling in colorectal cancer'. Together they form a unique fingerprint.

Cite this