Dataset Information

Differential expression of SUMO-specific protease 7 variants regulates epithelial-mesenchymal transition.

ABSTRACT: Two Sentrin/small ubiquitin-like modifier (SUMO)-specific protease 7 (SENP7) variants are naturally expressed in breast epithelia. Breast cancer (BCa) onset down-regulates the short SENP7 splice variant (SENP7S) and enhances the long transcript (SENP7L). Here, we show that SENP7L induction promotes gene expression profiles that favor aberrant proliferation and initiate epithelial-mesenchymal transition (EMT). SENP7L exhibits an interaction domain for the epigenetic remodeler heterochromatin protein 1 ? (HP1?) and isopeptidase activity against SUMO-modified HP1?. Loss of this interaction domain, as observed with SENP7S, favors HP1? SUMOylation. SUMOylated HP1? is enriched at E2F-responsive and mesenchymal gene promoters, silences transcription of these genes, and promotes cellular senescence. Elevated SENP7L renders HP1? hypo-SUMOylated, which relieves transcriptional repression of the same genes and concurrently decreases transcription of epithelial-promoting genes via an HP1?-independent mechanism. Consequently, SENP7L levels correlate with EMT, motility, and invasiveness of BCa cells. Stable knockdown of elevated SENP7L levels lessens the dissemination of highly metastatic BCa cells to the lungs from primary implantation sites in in vivo studies. Thus, differential splicing of the SENP7 regulates either tumor suppression or progression.

SUBMITTER: Bawa-Khalfe T

PROVIDER: S-EPMC3491469 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Differential expression of SUMO-specific protease 7 variants regulates epithelial-mesenchymal transition.

Bawa-Khalfe Tasneem T Lu Long-Sheng LS Zuo Yong Y Huang Chao C Dere Ruhee R Lin Feng-Ming FM Yeh Edward T H ET

Proceedings of the National Academy of Sciences of the United States of America 20121008 43

Two Sentrin/small ubiquitin-like modifier (SUMO)-specific protease 7 (SENP7) variants are naturally expressed in breast epithelia. Breast cancer (BCa) onset down-regulates the short SENP7 splice variant (SENP7S) and enhances the long transcript (SENP7L). Here, we show that SENP7L induction promotes gene expression profiles that favor aberrant proliferation and initiate epithelial-mesenchymal transition (EMT). SENP7L exhibits an interaction domain for the epigenetic remodeler heterochromatin prot ...[more]

PMID: 23045645

Similar Datasets

Project description:Epithelial-mesenchymal transition (EMT) involving down-regulation of E-cadherin is thought to play a fundamental role during early steps of invasion and metastasis of carcinoma cells. The aim of our study was to elucidate the role of EMT regulators Snail, SIP1 (both are direct repressors of E-cadherin), and Twist (an activator of N-cadherin during Drosophila embryogenesis), in primary human gastric cancers. Expression of Snail, SIP1, and Twist was analyzed in 48 gastric carcinomas by real-time quantitative RT-PCR in paraffin-embedded and formalin-fixed tissues. The changes of expression levels of these genes in malignant tissues compared to matched non-tumorous tissues were correlated with the expression of E- and N-cadherin. From 28 diffuse-type gastric carcinomas analyzed reduced E-cadherin expression was detected in 11 (39%) cases compared to non-tumorous tissues. Up-regulated Snail could be found in 6 cases with reduced or negative E-cadherin expression. However, there was no correlation to increased SIP1 expression. Interestingly, we could detect abnormal expression of N-cadherin mRNA in 6 cases, which was correlated with Twist overexpression in 4 cases. From 20 intestinal-type gastric cancer samples reduced E-cadherin expression was found in 12 (60%) cases, which was correlated to up-regulation of SIP1, since 10 of these 12 cases showed elevated mRNA levels, whereas Snail, Twist, and N-cadherin were not up-regulated. We present the first study investigating the role of EMT regulators in human gastric cancer and provide evidence that an increase in Snail mRNA expression is associated with down-regulation of E-cadherin in diffuse-type gastric cancer. We detected abnormally positive or increased N-cadherin mRNA levels in the same tumors, probably due to overexpression of Twist. SIP1 overexpression could not be linked to down-regulated E-cadherin in diffuse-type tumors, but was found to be involved in the pathogenesis of intestinal-type gastric carcinoma. We conclude that EMT regulators play different roles in gastric carcinogenesis depending on the histological subtype.

Dataset Information

Differential expression of SUMO-specific protease 7 variants regulates epithelial-mesenchymal transition.

Publications

Differential expression of SUMO-specific protease 7 variants regulates epithelial-mesenchymal transition.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets