Functional significance of Hippo/YAP signaling for drug resistance in colorectal cancer

Ruolan Song, Dongsheng Gu, Lining Zhang, Xiaoli Zhang, Beiqin Yu, Bingya Liu, Jingwu Xie

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Colorectal cancer is a leading cause of cancer-related death worldwide. While early stage colorectal cancer can be removed by surgery, patients with advanced disease are treated by chemotherapy, with 5-Fluorouracil (5-FU) as a main ingredient. However, most patients with advanced colorectal cancer eventually succumb to the disease despite some responded initially. Thus, identifying molecular mechanisms responsible for drug resistance will help design novel strategies to treat colorectal cancer. In this study, we analyzed an acquired 5-FU resistant cell line, LoVo-R, and determined that elevated expression of YAP target genes is a major alteration in the 5-FU resistant cells. Hippo/YAP signaling, a pathway essential for cell polarity, is an important regulator for tissue homeostasis, organ size, and stem cells. We demonstrated that knockdown of YAP1 sensitized LoVo-R cells to 5-FU treatment in cultured cells and in mice. The relevance of our studies to colorectal cancer patients is reflected by our discovery that high expression of YAP target genes in the tumor was associated with an increased risk of cancer relapse and poor survival in a larger cohort of colorectal cancer patients who underwent 5-FU-related chemotherapy. Taken together, we demonstrate a critical role of YAP signaling for drug resistance in colorectal cancer.

Original languageEnglish (US)
Pages (from-to)1608-1615
Number of pages8
JournalMolecular Carcinogenesis
Volume57
Issue number11
DOIs
StatePublished - Nov 2018

Keywords

  • 5-fluorouracil (5-FU)
  • YAP
  • cancer therapy
  • colorectal cancer
  • drug resistance

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

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