ZNF750 is a lineage-specific tumour suppressor in squamous cell carcinoma

被引：100

作者：

Hazawa, M. ^{[1
,2
]}

Lin, D-C ^{[1
,3
]}

Handral, H. ^{[4
]}

Xu, L. ^{[1
]}

Chen, Y. ^{[1
]}

Jiang, Y-Y ^{[1
]}

Mayakonda, A. ^{[1
]}

Ding, L-W ^{[1
]}

Meng, X. ^{[1
]}

Sharma, A. ^{[1
]}

Samuel, S. ^{[1
]}

Movahednia, M. M. ^{[4
]}

Wong, R. W. ^{[2
]}

Yang, H. ^{[1
]}

Tong, C. ^{[4
]}

Koeffler, H. P. ^{[1
,3
,5
,6
]}

机构：

[1] Natl Univ Singapore, Canc Sci Inst Singapore, Singapore, Singapore

[2] Kanazawa Univ, Inst Frontier Sci Initiat, Cell Bion Res Unit, Innovat Integrated Biores Core, Kanazawa, Ishikawa, Japan

[3] Univ Calif Los Angeles, Sch Med, Div Hematol Oncol, Cedars Sinai Med Ctr, Los Angeles, CA 90024 USA

[4] Natl Univ Singapore, Dept Oral & Maxillofacial Surg, Fac Dent, Singapore, Singapore

[5] Natl Univ Hlth Syst, Natl Univ Canc Inst, Singapore, Singapore

[6] Natl Univ Singapore, Singapore, Singapore

来源：

ONCOGENE | 2017年 / 36卷 / 16期

基金：

英国医学研究理事会;

关键词：

D O I：

10.1038/onc.2016.377

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

ZNF750 controls epithelial homeostasis by regulating epidermal-differentiation genes, a role underscored by its pathogenic mutations in esophageal squamous cell cancers (SCCs). However, the precise role of ZNF750 in SCC cell biology remains unclear. In this study, we report that ZNF750 is exclusively deleted, mutated and underexpressed in human SCCs, and low ZNF750 expression is associated with poor survival. Restoration of wildtype, but not mutant ZNF750 protein uniquely inhibited the malignant phenotypes of SCC cells both in vitro and in vivo. Notably, ZNF750 promoted the expression of a long non-coding RNA (TINCR), which mediated both cancer-inhibition and differentiation-induction effects of ZNF750. In addition, ZNF750 potently suppressed cell migration by directly inhibiting the transactivation of LAMC2. Together, our findings characterize ZNF750 as a crucial SCC-specific suppressor and uncover its novel anticancer-associated functions.

引用

页码：2243 / 2254

页数：12

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