HMGCR is necessary for the tumorigenecity of esophageal squamous cell carcinoma and is regulated by Myc

被引：35

作者：

Zhong, Chenxi ^{[1
]}

Fan, Limin ^{[1
]}

Yao, Feng ^{[1
]}

Shi, Jianxin ^{[1
]}

Fang, Wentao ^{[1
]}

Zhao, Heng ^{[1
]}

机构：

[1] Shanghai Jiao Tong Univ, Dept Thorac Surg, Shanghai Chest Hosp, Shanghai 200030, Peoples R China

来源：

TUMOR BIOLOGY | 2014年 / 35卷 / 05期

基金：

上海市自然科学基金;

关键词：

HMGCR; ESCC; Cell growth; Cell migration; Myc; POOR-PROGNOSIS; CANCER; GROWTH;

D O I：

10.1007/s13277-013-1539-8

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Hydroxymethylglutaryl coenzyme A reductase (HMGCR), the rate-limiting enzyme of mevalonate pathway, has been involved in the tumorigenesis of several tumor types. Our previous study has showed that statin, the inhibitor of HMGCR, inhibited the tumorigenecity of esophageal squamous cell carcinoma (ESCC) in vitro and in vivo. However, the function of HMGCR in the carcinogenesis of ESCC cells remains unknown. In this study, we have observed the up-regulation of HMGCR in ESCC tissues compared with the paired normal tissues. Over-expression of HMGCR in ESCC cells promoted cell growth and migration, while knockdown of the expression of HMGCR inhibited the growth, migration and colony formation of ESCC cells in vitro and in vivo. Furthermore, we found that oncogene Myc positively regulated the expression of HMGCR. Taken together, our study revealed the pivotal function of HMGCR and mevalonate pathway in the progression of ESCC and supported the clinical application of statin.

引用

页码：4123 / 4129

页数：7

共 18 条

[1] A novel statin-mediated "prenylation block-and-release" assay provides insight into the membrane targeting mechanisms of small GTPases [J].

Ali, Bassam R. ;

Nouvel, Ian ;

Leung, Ka Fai ;

Hume, Alistair N. ;

Seabra, Miguel C. .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2010, 397 (01) :34-41

[2] The SREBP pathway: Regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor [J].

Brown, MS ;

Goldstein, JL .

CELL, 1997, 89 (03) :331-340

[3] MYC Phosphorylation, Activation, and Tumorigenic Potential in Hepatocellular Carcinoma Are Regulated by HMG-CoA Reductase [J].

Cao, Zhongwei ;

Fan-Minogue, Hua ;

Bellovin, David I. ;

Yevtodiyenko, Aleksey ;

Arzeno, Julia ;

Yang, Qiwei ;

Gambhir, Sanjiv Sam ;

Felsher, Dean W. .

CANCER RESEARCH, 2011, 71 (06) :2286-2297

[4] Statin use and breast cancer: Prospective results from the Women's Health Initiative [J].

Cauley, JA ;

McTiernan, A ;

Rodabough, RJ ;

LaCroix, A ;

Bauer, DC ;

Margolis, KL ;

Paskett, ED ;

Vitolins, MZ ;

Furberg, CD ;

Chlebowski, RT .

JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2006, 98 (10) :700-707

[5] Safety profiles for the HMG-CoA reductase inhibitors - Treatment and trust [J].

Davidson, MH .

DRUGS, 2001, 61 (02) :197-206

[6] The biology of cancer: Metabolic reprogramming fuels cell growth and proliferation [J].

DeBerardinis, Ralph J. ;

Lum, Julian J. ;

Hatzivassiliou, Georgia ;

Thompson, Craig B. .

CELL METABOLISM, 2008, 7 (01) :11-20

[7] REGULATION OF THE MEVALONATE PATHWAY [J].

GOLDSTEIN, JL ;

BROWN, MS .

NATURE, 1990, 343 (6257) :425-430

[8] STRUCTURE OF THE HUMAN GENE ENCODING STEROL REGULATORY ELEMENT-BINDING PROTEIN-1 (SREBF1) AND LOCALIZATION OF SREBF1 AND SREBF2 TO CHROMOSOMES 17P11.2 AND 22Q13 [J].

HUA, XX ;

WU, J ;

GOLDSTEIN, JL ;

BROWN, MS ;

HOBBS, HH .

GENOMICS, 1995, 25 (03) :667-673

[9]

Jackson S M, 1997, Subcell Biochem, V28, P1

[10] Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis [J].

Menendez, Javier A. ;

Lupu, Ruth .

NATURE REVIEWS CANCER, 2007, 7 (10) :763-777

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