p62/sequestosome 1 in human colorectal carcinoma as a potent prognostic predictor associated with cell proliferation

Shun Nakayama, Hideaki Karasawa, Takashi Suzuki, Shinichi Yabuuchi, Kiyoshi Takagi, Takashi Aizawa, Yoshiaki Onodera, Yasuhiro Nakamura, Mika Watanabe, Fumiyoshi Fujishima, Hiroshi Yoshida, Takanori Morikawa, Tomohiko Sase, Takeshi Naitoh, Michiaki Unno, Hironobu Sasano

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

p62/sequestosome 1 (p62) is a multi-domain protein that functions as a receptor for ubiquitinated targets in the selective autophagy and serves as a scaffold in various signaling cascades. p62 have been reported to be up-regulated in several human malignancies, but the biological roles and significance of p62 are still poorly understood in colorectal carcinoma. We immunohistochemically evaluated p62 in 118 colorectal adenocarcinoma and 28 colorectal adenoma cases. We used four colon carcinoma cells (HCT8, HT29, COLO320, and SW480) in the in vitro studies. p62 immunoreactivity was detected in 11% of colorectal adenoma cases and 31% of adenocarcinoma cases, while it was negligible in the normal epithelium. The immunohistochemical p62 status was significantly associated with synchronous liver metastasis, and it turned out to be an independent adverse prognostic factor in colorectal cancer patients. Following in vitro studies revealed that HCT8 and HT29 cells transfected with p62-specific siRNA showed significantly decreased cell proliferation activity, whereas COLO320 and SW480 cells transfected with p62 expression plasmid showed significantly increased cell proliferation activity. The p62-mediated cell proliferation was not associated with the autophagy activity. These findings suggest that p62 promotes the cell proliferation mainly as a scaffold protein, and that the p62 status is a potent prognostic factor in colorectal carcinoma patients.

Original languageEnglish
Pages (from-to)1264-1274
Number of pages11
JournalCancer medicine
Volume6
Issue number6
DOIs
Publication statusPublished - 2017 Jun

Keywords

  • Cell proliferation
  • colorectal carcinoma
  • immunohistochemistry
  • p62
  • prognosis

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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