This study aims to clarify the function of transient receptor potential melastatin 8 (TRPM8) in colon cancer liver metastasis. First, TRPM8 expression was determined by Western blotting in colon cancer patients with/without liver metastasis. Second, colon cancer cells were grouped into Mock, siCON, and siTRPM8 groups. Then, a series of in vitro experiments were conducted. Last, CT26 cells were used to construct colon cancer liver metastasis models on mice in vivo, followed by comparison of liver metastasis and determination of AKT/glycogen synthase kinase-3β (GSK-3β) pathway. Consequently, TRPM8 was upregulated in both colon cancer patients with/without liver metastasis, especially in those with metastasis. Compared with Mock and siCON groups, cells in siTRPM8 group demonstrated significant decreases in clone numbers, cell invasion, and migration; and obvious downregulations of p-AKT/AKT, p-GSK3β/GSK3β, Snail, and Vimentin, with an upregulation of E-cadherin. For in vivo experiments, a sharp decrease was observed in metastatic liver of mice in siTRPM8 group, with significant downregulations of p-AKT/AKT, p-GSK3β/GSK3β, Snail, and Vimentin and an upregulation of E-cadherin, as compared with Mock and siCON groups. Thus, TRPM8 was upregulated in colon cancer patients with liver metastasis, and silencing TRPM8 may suppress the progression and epithelial–mesenchymal transition of colon cancer cells to block its liver metastasis possibly by inhibiting AKT/GSK-3β pathway.

中文翻译：

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TRPM8上调可通过介导Akt/GSK-3信号通路促进结肠癌肝转移

本研究旨在阐明瞬时受体电位melastatin 8 (TRPM8) 在结肠癌肝转移中的作用。首先，通过蛋白质印迹在有/无肝转移的结肠癌患者中确定 TRPM8 表达。其次，将结肠癌细胞分为 Mock、siCON 和 siTRPM8 组。然后，进行了一系列体外实验。最后，利用CT26细胞在体内构建小鼠结肠癌肝转移模型，比较肝转移情况并测定AKT/糖原合酶激酶-3β（GSK-3β）通路。因此，TRPM8 在有/无肝转移的结肠癌患者中上调，尤其是在有转移的结肠癌患者中。与 Mock 和 siCON 组相比，siTRPM8 组的细胞克隆数、细胞侵袭和迁移显着减少；p-AKT/AKT、p-GSK3β/GSK3β、Snail 和 Vimentin 明显下调，而 E-cadherin 上调。对于体内实验，与 siTRPM8 组相比，在 siTRPM8 组小鼠的转移性肝脏中观察到急剧下降，p-AKT/AKT、p-GSK3β/GSK3β、Snail 和 Vimentin 显着下调，而 E-cadherin 上调。 Mock 和 siCON 组。因此，TRPM8 在结肠癌肝转移患者中上调，并且沉默TRPM8可能通过抑制AKT/GSK-3β通路抑制结肠癌细胞的进展和上皮-间质转化，从而阻断其肝转移。