Targeting FER Kinase Inhibits Melanoma Growth and Metastasis

被引：14

作者：

Ivanova, Iordanka A. ^{[1
,2
,3
]}

Arulanantham, Shinthujah ^{[1
,2
,3
]}

Barr, Kevin ^{[1
]}

Cepeda, Mario ^{[4
]}

Parkins, Katie M. ^{[5
,6
]}

Hamilton, Amanda M. ^{[5
,6
]}

Johnston, Danielle ^{[7
]}

Penuela, Silvia ^{[7
,8
]}

Hess, David A. ^{[1
,6
]}

Ronald, John A. ^{[5
,6
]}

Dagnino, Lina ^{[1
,2
,3
,8
]}

机构：

[1] Univ Western Ontario, Dept Physiol & Pharmacol, London, ON N6A 5C1, Canada

[2] Univ Western Ontario, Childrens Hlth Res Inst, London, ON N6C 2V5, Canada

[3] Univ Western Ontario, Lawson Hlth Res Inst, London, ON N6C 2R5, Canada

[4] Mayo Clin, Dept Urol, Rochester, MN 55902 USA

[5] Univ Western Ontario, Dept Med Biophys, London, ON N6A 5C1, Canada

[6] Univ Western Ontario, Robarts Res Inst, London, ON N6A 5B7, Canada

[7] Univ Western Ontario, Dept Anat & Cell Biol, London, ON N6A 5C1, Canada

[8] Univ Western Ontario, Dept Oncol, London, ON N6A 5C1, Canada

来源：

CANCERS | 2019年 / 11卷 / 03期

基金：

加拿大健康研究院;

关键词：

FER; tyrosine kinase; metastasis; tumor invasion; BETA-CATENIN REQUIRES; ADHESION MOLECULE L1; CELL-MIGRATION; TYROSINE; PHOSPHORYLATION; MODEL; ACTIVATION; INVASION; GENE; TRANSCRIPTION;

D O I：

10.3390/cancers11030419

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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/beta-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.

引用

页数：22

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