Laboratory of Molecular Disease and Cell Regulation, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, Incheon, Korea.
Carcinogenesis. 2010 Nov;31(11):1939-47. doi: 10.1093/carcin/bgq180. Epub 2010 Aug 28.
Tropomyosin-related kinase (Trk) C, a member of the Trk family of neurotrophin receptors, has been implicated in the growth and survival of human cancer tissues. Here, we report that TrkC is frequently overexpressed in human breast cancers and plays an essential role in tumor growth and metastasis. Ectopic expression of TrkC in non-malignant mammary epithelial cells suppressed anoikis, which correlated with activation of the Ras-mitogen-activated protein kinase and phosphatidylinositol-3-OH kinase (PI3K)/Akt pathways, and reduced expression of the metastatic regulator Twist. Furthermore, suppression of TrkC expression in highly metastatic mammary carcinoma cells inhibited their growth in vitro, as well as their ability to metastasize from the mammary gland to the lung in vivo. These results have identified TrkC as a critical regulator of breast cancer cell growth and metastasis.
原肌球蛋白相关激酶 (Trk) C 是神经营养因子受体 Trk 家族的成员之一，与人类癌症组织的生长和存活有关。在这里，我们报告 TrkC 在人类乳腺癌中经常过表达，并在肿瘤生长和转移中发挥重要作用。TrkC 在非恶性乳腺上皮细胞中的异位表达抑制了失巢凋亡，这与 Ras-丝裂原活化蛋白激酶和磷脂酰肌醇-3-羟基激酶 (PI3K)/Akt 途径的激活以及转移性调节剂 Twist 的表达降低有关。此外，在高转移性乳腺癌细胞中抑制 TrkC 的表达，抑制了它们在体外的生长，以及它们在体内从乳腺转移到肺部的能力。这些结果表明 TrkC 是乳腺癌细胞生长和转移的关键调节因子。
