Ivanova Iordanka A, Arulanantham Shinthujah, Barr Kevin, Cepeda Mario, Parkins Katie M, Hamilton Amanda M, Johnston Danielle, Penuela Silvia, Hess David A, Ronald John A, Dagnino Lina
Department of Physiology and Pharmacology, University of Western Ontario, London, ON N6A 5C1, Canada.
Children's Health Research Institute, University of Western Ontario, London, ON N6C 2V5, Canada.
Cancers (Basel). 2019 Mar 24;11(3):419. doi: 10.3390/cancers11030419.
Melanoma is one of the most aggressive types of tumors and exhibits high metastatic potential. Fes-related (FER) kinase is a non-receptor tyrosine kinase that has been implicated in growth and metastasis of various epithelial tumors. In this study, we have examined the role that FER kinase plays in melanoma at the molecular level. FER-depleted melanoma cells exhibit impaired Wnt/β-catenin pathway activity, as well as multiple proteomic changes, which include decreased abundance of L1-cell adhesion molecule (L1-CAM). Consistent with the pro-metastatic functions of these pathways, we demonstrate that depletion of FER kinase decreases melanoma growth and formation of distant metastases in a xenograft model. These findings indicate that FER is an important positive regulator of melanoma metastasis and a potential target for innovative therapies.
黑色素瘤是最具侵袭性的肿瘤类型之一，具有很高的转移潜能。Fes相关（FER）激酶是一种非受体酪氨酸激酶，已被证明与多种上皮肿瘤的生长和转移有关。在本研究中，我们在分子水平上研究了FER激酶在黑色素瘤中所起的作用。FER缺失的黑色素瘤细胞表现出Wnt/β-连环蛋白信号通路活性受损，以及多种蛋白质组学变化，其中包括L1细胞粘附分子（L1-CAM）丰度降低。与这些信号通路的促转移功能一致，我们证明在异种移植模型中，FER激酶的缺失会降低黑色素瘤的生长和远处转移的形成。这些发现表明，FER是黑色素瘤转移的重要正向调节因子，也是创新疗法的潜在靶点。
