PRSS8 suppresses colorectal carcinogenesis and metastasis

Yonghua Bao, Yongchen Guo, Yiqiong Yang, Xiaonan Wei, Shanshan Zhang, Yongmeng Zhang, Kai Li, Ming Yuan, Dongli Guo, Virgilia Macias, Xiangdong Zhu, Wei Zhang, Wancai Yang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

The serine protease PRSS8 has shown important physiological and pathological functions, but its roles in cancer initiation and progression are unclear. We developed and dynamically characterized a conditional knockout Prss8fl/fl, p-Villin-Cre+ mouse model. We found that genetic deficiency of the Prss8 gene caused spontaneous colitis and an inflamed rectum at an early age and caused intestinal tumors at a late age, which were linked to increased intestinal cell proliferation and migration but decreased cell differentiation. Increased PRSS8 expression inhibited cancer cell growth and metastasis in nude mice and inhibited cancer cell migration, invasion, colony formation and tumor sphere formation in vitro, but decreased PRSS8 expression facilitated malignancies in vivo and in vitro. Gene profiling on manipulated cancer cells and intestinal epithelial cells of Prss8 mouse models, gene set enrichment analysis and mechanistic studies revealed that PRSS8 targeted the Wnt/β-catenin, epithelial-mesenchymal transition, and stem cell signaling pathways, which were further supported by the results from the TCGA data mining and validated by immunohistochemical staining on colorectal cancer tissue microarrays. In conclusion, PRSS8 is a novel tumor suppressor that plays critical roles in the suppression of colorectal carcinogenesis and metastasis.

Original languageEnglish (US)
Pages (from-to)497-517
Number of pages21
JournalOncogene
Volume38
Issue number4
DOIs
StatePublished - Jan 24 2019

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Fingerprint

Dive into the research topics of 'PRSS8 suppresses colorectal carcinogenesis and metastasis'. Together they form a unique fingerprint.

Cite this