Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1522282 (EMT)
 2,868 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tspan8 and CD151 are metastasis-promoting tetraspanins and a knockdown (kd) of Tspan8 or CD151 and most pronounced of both tetraspanins affects the metastatic potential of the rat pancreatic adenocarcinoma line ASML. Approaching to elaborate the underlying mechanism, we compared ASMLwt, -CD151kd and/or Tspan8kd clones. We focused on tumor exosomes, as exosomes play a major role in tumor progression and tetraspanins are suggested to be engaged in exosome targeting. ASML-CD151/Tspan8kd cells poorly metastasize, but regain metastatic capacity, when rats are pretreated with ASMLwt, but not ASML-CD151kd and/or -Tspan8kd exosomes. Both exosomal CD151 and Tspan8 contribute to host matrix remodelling due to exosomal tetraspanin-integrin and tetraspanin-protease associations. ASMLwt exosomes also support stroma cell activation with upregulation of cytokines, cytokine receptors and proteases and promote inflammatory cytokine expression in hematopoietic cells. Finally, CD151-/Tspan8-competent exosomes support EMT gene expression in poorly-metastatic ASML-CD151/Tspan8kd cells. These effects are not seen or are weakened using ASML-CD151kd or -Tspan8kd exosomes, which is at least partly due to reduced binding/uptake of CD151- and/or Tspan8-deficient exosomes. Thus, CD151- and Tspan8-competent tumor exosomes support matrix degradation, reprogram stroma and hematopoietic cells and drive non-metastatic ASML-CD151/Tspan8kd cells towards a motile phenotype.
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PMID:The tetraspanins CD151 and Tspan8 are essential exosome components for the crosstalk between cancer initiating cells and their surrounding. 2554 74

Background: Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype. G protein coupled receptor (GPER), the key player in the intercellular signaling communication, has been verified to participate in tumorigenesis. The present study aims to explore the effects of GPER on cell proliferation, invasion and EMT through CD151/miR-199a-3p bio-axis in TNBC cells. Methods: Total proteins were isolated from TNBC cell lines and GPER expression was determined using western blot assay. CCK-8 assay was used to detect cell viability after being treated with GPER activation. Western blotting and immunofluorescence were applied to measure the level of proteins associated with cell proliferation, angiogenesis and EMT, as well as the Hippo signal pathway. The level of miR-199a-3p and transfection efficiency were evaluated by reverse transcriptase quantitative PCR (RT-qPCR) after being transfected with miR-199a-3p mimics. Cell migration and invasion of TNBC cells were assessed by wound healing and transwell assays. Moreover, luciferase reporter assay was conducted to verify the relationship between CD151 and miR-199a-3p. Results: GPER activation treatment suppressed MDA-MB-231 cell viability, proliferation, migration, invasion, angiogenesis and EMT process. The expression of E-cadherin was increased, but N-cadherin, Vimentin, VEGFA, AngII and CD151 were decreased after GPER activation treatment. Conversely, inhibition of GPER indeed up-regulated CD151 expression. In addition, overexpression of miR-199a-3p supressed cell proliferation, migration, invasion and angiogenesis, as well as EMT process and the Hippo signal pathway. Conclusion: Collectively, the activation of GPER inhibits cells proliferation, invasion and EMT of triple-negative breast cancer via CD151/miR-199a-3p bio-axis. This study provides a novel intervention target for the treatment of breast cancer cells and a fresh idea for the clinical therapy of breast cancer.
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PMID:The activation of GPER inhibits cells proliferation, invasion and EMT of triple-negative breast cancer via CD151/miR-199a-3p bio-axis. 3205 35