TMEM16A overexpression contributes to tumor invasion and poor prognosis of human gastric cancer through TGF-β signaling.
TMEM16A overexpression contributes to tumor invasion and poor prognosis of human gastric cancer through TGF-β signaling.
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DOI：
10.18632/oncotarget.3412
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发表时间：
2015-05-10
期刊：
影响因子：
--
通讯作者：
Wang XG
中科院分区：
文献类型：
--
作者：
Liu F;Cao QH;Lu DJ;Luo B;Lu XF;Luo RC;Wang XG
TMEM 16 A是一种新发现的钙激活氯离子通道，在多种恶性实体瘤中过表达，可促进细胞增殖和侵袭，但其在胃癌中的作用尚不清楚。因此，我们通过对367例胃癌患者的回顾性分析，研究了TMEM 16 A在胃癌中的作用及其临床意义，并进行了体外研究以验证其作用及其分子机制。TMEM 16 A在胃癌组织中显著上调和扩增，其过表达与疾病分期呈正相关，与患者生存率呈负相关，并被鉴定为患者预后的独立预后因素。367例胃癌组织中TMEM 16 A与E-cadherin呈负相关。TMEM 16 A沉默显著降低钙激活氯电流，损害TGF-β分泌，降低E-钙粘蛋白表达，并抑制GC细胞（AGS和BGC-823）的迁移和侵袭，而不影响其增殖。TGF-β的补充逆转了TMEM 16 A沉默对E-cadherin表达、细胞迁移和侵袭的影响。TMEM 16 A基因可能是胃癌的一个新的生物学标志物和潜在的治疗靶点。
TMEM16A is a newly identified calcium activated chloride channel, and has been reported to be overexpressed by various solid malignant cancers to promote proliferation and invasion, yet little is known about its role in gastric cancer(GC). Therefore, we investigated the role of TMEM16A in GC and its clinical significance by a retrospective analysis of 367 GC patients, and in vitro study was performed for validation and underlying molecular mechanism. TMEM16A was significantly upregulated and amplified in GC tissues, and its overexpression was positively correlated with disease stage, negatively with patient survival and identified as an independent prognostic factor for patient outcome. A negative correlation between TMEM16A and E-cadherin was found in 367 GC specimens. TMEM16A silencing significantly decreased calcium activated chloride currents, impaired TGF-β secretion, reduced E-cadherin expression, and inhibited the migration and invasion without affecting proliferation of GC cells (AGS and BGC-823). Supplement of TGF-β reverted the effects of TMEM16A silencing on E-cadherin expression, cell migration and invasion. In conclusion, TMEM16A promotes invasion and metastasis in GC, and might be a novel prognostic biomarker and potential therapeutic target in the treatment of GC.
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DOI：
10.1074/jbc.m114.549188
发表时间：
2014-04-18
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Bill A;Hall ML;Borawski J;Hodgson C;Jenkins J;Piechon P;Popa O;Rothwell C;Tranter P;Tria S;Wagner T;Whitehead L;Gaither LA
通讯作者：
Gaither LA
影响因子：
11.5
作者：
Shi, Zhi-Zhou;Shang, Li;Wang, Ming-Rong
通讯作者：
Wang, Ming-Rong
影响因子：
3.3
作者：
Lee B;Cho H;Jung J;Yang YD;Yang DJ;Oh U
通讯作者：
Oh U
影响因子：
82.9
作者：
Kononen, J;Bubendorf, L;Kallioniemi, OP
通讯作者：
Kallioniemi, OP
DOI：
10.1073/pnas.1200174109
发表时间：
2012-06-26
影响因子：
11.1
作者：
Perez-Cornejo, Patricia;Gokhale, Avanti;Faundez, Victor
通讯作者：
Faundez, Victor