title: KCNN4 channels participate in the EMT induced by PRL-3 in colorectal cancer.
abstract: Studies have shown that phosphatase of regenerating liver-3 (PRL-3) promotes the invasion, migration, and metastasis of human tumor cells by facilitating an epithelial-mesenchymal transition (EMT). However, the mechanism by which PRL-3 induces tumor cell EMT is unknown. Our previous research revealed that PRL-3 promotes LoVo cell proliferation by up-regulating KCNN4 channels. In the current study, we explored the mechanism by which PRL-3 mediates EMT. We demonstrated that PRL-3 induced the expression of KCNN4 channels, leading to EMT and the down-regulation of E-cadherin. Further studies revealed that KCNN4 channels increased intracellular calcium levels and activated components of cell signaling downstream of calcium, including CaM-kinase II and glycogen synthase kinase-3 beta (GSK-3 beta), which increased Snail expression. Inhibiting KCNN4 with siRNA and TRAM-34, a specific inhibitor, restored E-cadherin expression and inhibited Snail expression. These results implicated the up-regulation of KCNN4 channels in the PRL-3-mediated induction of EMT and promotion of cancer metastasis.
authors.affiliation: Department of Gastroenteropancreatic Surgery, The Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lai
authors.forename: Lu
authors.initials: L
authors.lastname: Liu
authors.forename: Yujie
authors.initials: Y
authors.lastname: Zeng
authors.forename: Heng
authors.initials: H
authors.lastname: Wu
authors.forename: Heyang
authors.initials: H
authors.lastname: Xu
authors.forename: Shuang
authors.initials: S
authors.lastname: Chen
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Chu
mesh_terms: D000704:Analysis of Variance; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D006651:Histocytochemistry; D006801:Humans; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D015820:Cadherins; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; C496923:KCNN4 protein, human; D009363:Neoplasm Proteins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D038362:Glycogen Synthase Kinase 3; C484730:PTP4A3 protein, human; D017027:Protein Tyrosine Phosphatases