Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumor metastasis is responsible for 90% of all cancer-related deaths. Epithelial to mesenchymal transition (EMT) is an important prerequisite for tumor metastasis. One of the important mediators of EMT and cancer progression in ovarian cancer is the vimentin protein. The objective of the current study was to evaluate the molecular mechanism that regulates vimentin expression in ovarian cancer cells. Vimentin was robustly induced in the ovarian cancer cell line SKOV-3 compared to normal ovarian epithelial cell line Moody and the induction was not due to transcriptional upregulation. Treatment with the proteasomal inhibitor MG-132 revealed that vimentin is actively degraded by the proteasome in Moody cells and stabilized in the SKOV-3 cell line. Mass spectrometric analysis of vimentin immunoprecipitate of MG-132 treated Moody cells revealed candidate ubiquitin ligases associated with vimentin. RNAi mediated silencing of the candidate ubiquitin in Moody cells and concurrent overexpression of the candidate ubiquitin ligases in SKOV-3 confirmed that TRIM56 is the ubiquitin ligase that is degrading vimentin in Moody cells. RNAi mediated silencing of TRIM56 in Moody cells and ectopic overexpression of TRIM56 in SKOV-3 cells, respectively, significantly up- and down-regulated in vitro migration and invasion in these cells. Analysis of TRIM56 transcript level and vimentin protein expression in 25 patients with ovarian carcinoma confirmed an inverse correlation between TRIM56 and vimentin expression. Cumulatively, our data reveals for the first time a novel post-translational regulatory mechanism of regulating vimentin expression, EMT, and metastatic progression in ovarian cancer cells.
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PMID:The ubiquitin ligase TRIM56 inhibits ovarian cancer progression by targeting vimentin. 2877 21

Breast cancer ranks no. 1 in women cancer worldwide, while 60-70% are estrogen receptor alpha positive. The estrogen selective modulators, such as tamoxifen, become the effective drugs for controlling ER alpha breast cancer progression. However, tamoxifen resistance will develop during long-time treatment and cancer progression. Thus, further understanding of ER alpha signaling becomes necessary for the improvement of breast cancer therapy. Here, we identify TRIM56 as a novel regulatory factor in ER alpha signaling. TRIM56 expression is positively correlated with ER alpha and PR in breast cancer samples and is related to poor prognosis in endocrine therapy patients. TRIM56 depletion significantly decreases ER alpha signaling activity and ER-alpha-positive breast cancer proliferation in vitro and in vivo. TRIM56 associates with AF1 domain of ER alpha via its WD40 domain in the cytoplasm. TRIM56 prolongs ER alpha protein stability, possibly through targeting ER alpha K63-linked ubiquitination. In conclusion, our study reveals an interesting posttranslational mechanism between TRIM56 and ER alpha in breast cancer progression. Targeting TRIM56 could be a promising approach for ER-alpha-positive breast cancer.
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PMID:Regulation of estrogen signaling and breast cancer proliferation by an ubiquitin ligase TRIM56. 3100 Jun 90