Unknown

Dataset Information

0

TGF-?1 induces epigenetic silence of TIP30 to promote tumor metastasis in esophageal carcinoma.


ABSTRACT: TGF-?1, a potent EMT (epithelial-mesenchymal transition) inducer present in the tumor microenvironment, is involved in the metastasis and progression of various carcinomas, including esophageal squamous cell carcinoma (ESCC). TIP30 (30kDa HIV-1 Tat interacting protein) is a putative tumor metastasis suppressor. Here, we found TIP30 was decreased in cells undergoing EMT induced by TGF-?1, an occurrence that was related to promoter hypermethylation. TGF-?1 induced TIP30 hypermethylation via increasing DNMT1 and DNMT3A expression, which could be restored by TGF-? antibodies. In our in vitro and in vivo studies, we showed that silence of TIP30 led to EMT, enhanced migrative and invasive abilities of ESCC cells, promoted tumor metastasis in xenografted mice; alternatively, overexpression of TIP30 inhibited TGF-?1-induced EMT, and metastatic abilities of ESCC cells. Mechanically, TIP30 silencing induced the nuclear translocation and transcriptional activation of ?-catenin in an AKT-dependent manner, which further resulted in the initiation of EMT. Consistently, TIP30 was frequently methylated and downregulated in ESCC patients. Loss of TIP30 correlated with nuclear ?-catenin and aberrant E-cadherin expression. TIP30 was a powerful marker in predicting the prognosis of ESCC. Taken together, our results suggest a novel and critical role of TIP30 involved in TGF-?1-induced activation of AKT/?-catenin signaling and ESCC metastasis.

SUBMITTER: Bu F 

PROVIDER: S-EPMC4385840 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

altmetric image

Publications

TGF-β1 induces epigenetic silence of TIP30 to promote tumor metastasis in esophageal carcinoma.

Bu Fangfang F   Liu Xing X   Li Jingjing J   Chen Shukun S   Tong Xin X   Ma Chunsheng C   Mao Hui H   Pan Fei F   Li Xiaoyan X   Chen Bo B   Xu Liyan L   Li Enmin E   Kou Geng G   Han Jun J   Guo Shangjing S   Zhao Jian J   Guo Yajun Y  

Oncotarget 20150201 4


TGF-β1, a potent EMT (epithelial-mesenchymal transition) inducer present in the tumor microenvironment, is involved in the metastasis and progression of various carcinomas, including esophageal squamous cell carcinoma (ESCC). TIP30 (30kDa HIV-1 Tat interacting protein) is a putative tumor metastasis suppressor. Here, we found TIP30 was decreased in cells undergoing EMT induced by TGF-β1, an occurrence that was related to promoter hypermethylation. TGF-β1 induced TIP30 hypermethylation via increa  ...[more]

Similar Datasets

| S-EPMC7986551 | biostudies-literature
| S-ECPF-GEOD-61354 | biostudies-other
| S-EPMC5596437 | biostudies-literature
| S-EPMC4302654 | biostudies-literature
| S-EPMC6332640 | biostudies-literature
| S-EPMC4294333 | biostudies-literature
| S-EPMC7889896 | biostudies-literature
2014-09-12 | E-GEOD-61354 | biostudies-arrayexpress
| S-EPMC4346533 | biostudies-literature
| S-EPMC6652011 | biostudies-literature