Cysteine-rich intestinal protein 1 suppresses apoptosis and chemosensitivity to 5-fluorouracil in colorectal cancer through ubiquitin-mediated Fas degradation

Autor:	Lijun Xu, Liang Zhao, Rui Zhou, Weibin Zhang, Xuegang Sun, Weidong Li, Lanzhi Zhang, Xueqing Yao
Jazyk:	angličtina
Rok vydání:	2019
Předmět:	0301 basic medicine Cancer Research Colorectal cancer Apoptosis lcsh:RC254-282 Mice 03 medical and health sciences 0302 clinical medicine Western blot Ubiquitin In vivo Cell Line Tumor medicine Animals Humans fas Receptor Cysteine-rich intestinal protein 1 Cell Proliferation TUNEL assay medicine.diagnostic_test biology Chemistry Cell growth Research LIM Domain Proteins FAS medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Xenograft Model Antitumor Assays Gene Expression Regulation Neoplastic MicroRNAs 030104 developmental biology Oncology Drug Resistance Neoplasm Cell culture 030220 oncology & carcinogenesis Proteolysis biology.protein Cancer research Fluorouracil Carrier Proteins Colorectal Neoplasms Chemoresistant
Zdroj:	Journal of Experimental & Clinical Cancer Research, Vol 38, Iss 1, Pp 1-14 (2019) Journal of Experimental & Clinical Cancer Research : CR
ISSN:	1756-9966
DOI:	10.1186/s13046-019-1117-z
Popis:	Background Cysteine-rich intestinal protein 1 (CRIP1) is highly expressed in human intestine and aberrantly expressed in several types of tumor. However, studies on CRIP1 are limited and its role on tumor development and progression remains controversial and elusive. Methods Immunohistochemistry was performed to evaluate the expression of CRIP1 in paired normal and colorectal tumor specimens, as well as colorectal cell lines. Functional assays, such as CCK8, TUNEL assay and in vivo tumor growth assay, were used to detect the proliferation, apoptosis and response to 5-FU of CRIP1. Western blot was used to analyze Fas-mediated pathway induced by CRIP1. Rescue experiments were performed to evaluate the essential role of CRIP1 for Fas-mediated apoptosis. Results We demonstrated that CRIP1 is overexpressed in CRC tissues compared with adjacent normal mucosa. CRIP1 could dramatically recover the 5-Fluorouracil (5-FU) inhibited CRC cell proliferation in vitro and stimulate the tumor formation of CRC in vivo, probably through inhibiting CRC cell apoptosis. Moreover, CRIP1 also dramatically recovered the 5-Fluorouracil (5-FU) induced tumor cell apoptosis in vitro. Further study demonstrated that CRIP1 down-regulated the expression of Fas protein and proteins related to Fas-mediated apoptosis. CRIP1 could interact with Fas protein and stimulate its ubiquitination and degradation. In addition, a negative correlation was detected between the expression of CRIP1 and Fas protein in most of the clinical human CRC samples. Conclusion The current research reveals a vital role of CRIP1 in CRC progression, which provide a novel target for clinical drug resistance of colorectal cancer and undoubtedly contributing to the therapeutic strategies in CRC. Electronic supplementary material The online version of this article (10.1186/s13046-019-1117-z) contains supplementary material, which is available to authorized users.
Databáze:	OpenAIRE
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