Jahidin Aisyah H, Stewart Teneale A, Thompson Erik W, Roberts-Thomson Sarah J, Monteith Gregory R
School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia; Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam Campus, Selangor, Malaysia.
School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia.
Biochem Biophys Res Commun. 2016 Sep 2;477(4):731-736. doi: 10.1016/j.bbrc.2016.06.127. Epub 2016 Jun 25.
Two-pore channel proteins, TPC1 and TPC2, are calcium permeable ion channels found localized to the membranes of endolysosomal calcium stores. There is increasing interest in the role of TPC-mediated intracellular signaling in various pathologies; however their role in breast cancer has not been extensively evaluated. TPC1 and TPC2 mRNA was present in all non-tumorigenic and tumorigenic breast cell lines assessed. Silencing of TPC2 but not TPC1 attenuated epidermal growth factor-induced vimentin expression in MDA-MB-468 breast cancer cells. This effect was not due to a general inhibition of epithelial to mesenchymal transition (EMT) as TPC2 silencing had no effect on epidermal growth factor (EGF)-induced changes on E-cadherin expression. TPC1 and TPC2 were also shown to differentially regulate cyclopiazonic acid (CPA)-mediated changes in cytosolic free Ca(2+). These findings indicate potential differential regulation of signaling processes by TPC1 and TPC2 in breast cancer cells.
双孔通道蛋白TPC1和TPC2是定位于内溶酶体钙库膜上的钙通透性离子通道。人们对TPC介导的细胞内信号传导在各种病理过程中的作用越来越感兴趣；然而，它们在乳腺癌中的作用尚未得到广泛评估。在所评估的所有非致瘤性和致瘤性乳腺癌细胞系中均存在TPC1和TPC2 mRNA。在MDA-MB-468乳腺癌细胞中，TPC2而非TPC1的沉默减弱了表皮生长因子诱导的波形蛋白表达。这种效应并非由于对上皮-间质转化（EMT）的普遍抑制，因为TPC2沉默对表皮生长因子（EGF）诱导的E-钙黏蛋白表达变化没有影响。TPC1和TPC2还显示出对环匹阿尼酸（CPA）介导的胞质游离Ca（2+）变化的差异调节。这些发现表明TPC1和TPC2在乳腺癌细胞中对信号传导过程可能存在差异调节。
