KCNN4 Channels participate in the EMT induced by PRL-3 in colorectal cancer
KCNN4 Channels participate in the EMT induced by PRL-3 in colorectal cancer
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KCNN4通道参与PRL-3诱导结直肠癌的EMT
DOI：
10.1007/s12032-013-0566-z
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发表时间：
2013-06-01
期刊：
影响因子：
3.4
通讯作者：
Chu, Zhonghua
中科院分区：
文献类型：
--
作者：
Lai, Wei;Liu, Lu;Chu, Zhonghua
研究表明，再生肝-3磷酸酶（PRL-3）通过促进上皮-间质转化（EMT），促进人类肿瘤细胞的侵袭、迁移和转移。然而，PRL-3诱导肿瘤细胞EMT的机制尚不清楚。我们之前的研究发现PRL-3通过上调KCNN4通道促进LoVo细胞增殖。在本研究中，我们探讨了PRL-3介导EMT的机制。我们证明PRL-3诱导KCNN4通道的表达，导致EMT和E-cadherin的下调。进一步的研究表明，KCNN4通道增加了细胞内钙水平，并激活了钙下游的细胞信号传导成分，包括CaM-kinase II和糖原合成酶激酶-3 β (GSK-3 β)，从而增加了Snail的表达。用siRNA和特异性抑制剂TRAM-34抑制KCNN4，恢复E-cadherin的表达，抑制Snail的表达。这些结果暗示了KCNN4通道在prl -3介导的EMT诱导和促进癌症转移过程中的上调。
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.