YAP is a candidate oncogene for esophageal squamous cell carcinoma

被引：213

作者：

Muramatsu, Tomoki ^{[1
,2
]}

Imoto, Issei ^{[1
,3
]}

Matsui, Takeshi ^{[4
,5
]}

Kozaki, Ken-ichi ^{[1
,6
]}

Haruki, Shigeo ^{[1
,7
]}

Sudol, Marius ^{[8
]}

Shimada, Yutaka ^{[9
]}

Tsuda, Hitoshi ^{[6
,10
]}

Kawano, Tatsuyuki ^{[7
]}

Inazawa, Johji ^{[1
,2
,6
]}

机构：

[1] Tokyo Med & Dent Univ, Med Res Inst, Dept Mol Cytogenet, Bunkyo Ku, Tokyo 1138510, Japan

[2] Tokyo Med & Dent Univ, Global Ctr Excellence Program Frontier Res Mol De, Tokyo 1138510, Japan

[3] Univ Tokushima, Grad Sch, Inst Hlth Biosci, Dept Human Genet & Publ Hlth, Tokushima 7708503, Japan

[4] Tokyo Med & Dent Univ, Med Res Inst, Med Top Track Program, Tokyo 1138510, Japan

[5] Tokyo Med & Dent Univ, Sch Biomed Sci, Tokyo 1138510, Japan

[6] Tokyo Med & Dent Univ, Hard Tissue Genome Res Ctr, Tokyo 1138510, Japan

[7] Tokyo Med & Dent Univ, Dept Surg, Grad Sch, Tokyo 1138510, Japan

[8] Weis Ctr Res, Geisinger Clin, Lab Signal Transduct & Prote Profiling, Danville, PA 17822 USA

[9] Toyama Univ, Dept Surg & Sci, Grad Sch Med & Pharmaceut Sci Res, Toyama 9300194, Japan

[10] Natl Canc Ctr, Clin Lab Div, Tokyo 1040045, Japan

来源：

CARCINOGENESIS | 2011年 / 32卷 / 03期

关键词：

YES-ASSOCIATED PROTEIN; TUMOR-SUPPRESSOR; HIPPO PATHWAY; CONTACT INHIBITION; SIZE-CONTROL; ORGAN SIZE; PROLIFERATION; IDENTIFICATION; GENE; P73;

D O I：

10.1093/carcin/bgq254

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Yes-associated protein (YAP), the nuclear effector of the Hippo pathway, is a key regulator of organ size and a candidate human oncogene located at chromosome 11q22. Since we previously reported amplification of 11q22 region in esophageal squamous cell carcinoma (ESCC), in this study we focused on the clinical significance and biological functions of YAP in this tumor. Frequent overexpression of YAP protein was observed in ESCC cells including those with a robust amplicon at position 11q22. Overexpression of the YAP protein was frequently detected in primary tumors of ESCC as well. Patients with YAP-overexpressing tumors had a worse overall rate of survival than those with non-expressing tumors, and YAP positivity was independently associated with a worse outcome in the multivariate analysis. Further analyses in cells in which YAP was either overexpressed or depleted confirmed that cell proliferation was promoted in a YAP isoform-independent but YAP expression level-dependent manner. YAP depletion inhibited cell proliferation mainly in the G(0)-G(1) phase and induced an increase in CDKN1A/p21 transcription but a decrease in BIRC5/survivin transcription. Our results indicate that YAP is a putative oncogene in ESCC and it represents a potential diagnostic and therapeutic target.

引用

页码：389 / 398

页数：10

共 38 条

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