In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 74, No. 19_Supplement ( 2014-10-01), p. 4733-4733
Abstract:
p62/sequestosome 1 (p62) is a multi-domain protein implicated in the selective degradation of ubiquitinated protein by autophagy, and it also functions as a scaffold protein in cell signaling pathways. p62 was recently reported to be accumulated in several types of human cancer cells, but the clinical significance and biological roles of p62 have remained largely unknown in colorectal carcinoma. p62 immunoreactivity was examined in 118 surgical specimens of human colorectal carcinomas using immunohistochemistry. p62 immunoreactivity was detected in about one third of the carcinoma cases, while it was negligible in the adjacent non-neoplastic epithelium. The immunohistochemical p62 status was significantly associated with synchronous liver metastasis in the carcinoma cases, and multivariate analysis further revealed the p62 status as an independent adverse prognostic factor for overall survival in the patients. We used 4 colon carcinoma cells in the in vitro studies to evaluate the functional roles of p62. The colon carcinoma cells transfected with p62-specific small interfering RNAs showed significantly decreased cell proliferation activities, and the colon carcinoma cells transfected with p62 expression plasmid showed significantly increased the cell proliferation activity. Results of in vitro studies indicated that p62 significantly promoted the cell proliferation of colorectal carcinoma cells, but the autophagic activity was not linked to the p62-mediated cell proliferation. These findings suggest that p62 promotes the proliferation of colon carcinoma cells mainly as a scaffold protein. The p62 status is a potent prognostic factor in human colorectal cancer patients, and could be an important specific therapeutic target of colorectal carcinoma that could improve the clinical outcome in the future. Citation Format: Shun Nakayama, Takashi Suzuki, Shinichi Yabuuchi, Kiyoshi Takagi, Yoshiaki Onodera, Yasuhiro Nakamura, Mika Watanabe, Fumiyoshi Fujishima, Hiroshi Yoshida, Takanori Morikawa, Hideaki Karasawa, Tomohiko Sase, Takeshi Naitoh, Yu Katayose, Shinichi Egawa, Michiaki Unno, Hironobu Sasano. p62/sequestosome 1, a potent prognostic factor, enhance cell proliferation in human colorectal carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4733. doi:10.1158/1538-7445.AM2014-4733
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2014-4733
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2014
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
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