据一项发表在Cancer Research杂志上的最新研究证实,蛋白质瞬时感受器电位m7通道(TRPM7)是乳腺癌细胞转移的一个关键因子。研究发现,至少在乳腺癌转移异种移植模型中,TRPM7对转移是必须的,虽然这个发现不会有直接影响对病人的治疗,但他们相信这项新发现为癌症治疗开辟了新思路。
肿瘤转移的关键是原肿瘤部位肿瘤细胞粘附和迁移能力的变化。而TRPM7被证实参与调节细胞粘附和迁移过程,荷兰阿姆斯特丹癌症研究所的研究人员着手调查是否TRMP7能促进癌细胞转移。
他们评估TRPM7的基因表达水平是否与乳腺癌的进展密切相关。从诊断患有原发性乳腺肿瘤368名妇女得到的肿瘤组织发现TRPM7基因高表达水平与疾病的复发和远处转移发生显著相关。
研究能够证明TRPM7高表达水平是这些妇女患者预后的独立预测,但这是否能用于预测病人的预后有待进一步验证。该项研究结果表明,抑制TRPM7能导致乳腺癌细胞体外迁移能力下降,小鼠体内转移潜能亦降低。
研究人员工作假设是,TRPM7在乳腺癌细胞和它们环境之间的相互作用中有关键作用。乳腺癌细胞对环境因素非常敏感。科研人员认为,但尚未有没有证明TRPM7通道传感器促使乳腺癌细胞能更加感知环境的变化。(生物谷:Bioon.com)
编译自:TRPM7 Protein Key to Breast Cancer Metastasis in Animal Models
doi:10.1158/0008-5472.CAN-11-3863
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TRPM7 Is Required for Breast Tumor Cell Metastasis.
Jeroen Middelbeek, Arthur J. Kuipers, Linda Henneman, Daan Visser, Ilse Eidhof, Remco van Horssen, Bé Wieringa, Sander V. Canisius, Wilbert Zwart, Lodewyk F. Wessels, Fred C.G.J. Sweep, Peter Bult, Paul N. Span, Frank N. van Leeuwen, and Kees Jalink.
TRPM7 encodes a Ca2+-permeable nonselective cation channel with kinase activity. TRPM7 has been implicated in control of cell adhesion and migration, but whether TRPM7 activity contributes to cancer progression has not been established. Here we report that high levels of TRPM7 expression independently predict poor outcome in breast cancer patients and that it is functionally required for metastasis formation in a mouse xenograft model of human breast cancer. Mechanistic investigation revealed that TRPM7 regulated myosin II–based cellular tension, thereby modifying focal adhesion number, cell–cell adhesion and polarized cell movement. Our findings therefore suggest that TRPM7 is part of a mechanosensory complex adopted by cancer cells to drive metastasis formation.