Targeting FER Kinase Inhibits Melanoma Growth and Metastasis

Iordanka A Ivanova; Shinthujah Arulanantham; Kevin Barr; Mario Cepeda; Katie M Parkins; Amanda M Hamilton; Danielle Johnston; Silvia Penuela; David A Hess; John A Ronald; Lina Dagnino

doi:10.3390/cancers11030419

Targeting FER Kinase Inhibits Melanoma Growth and Metastasis

Cancers (Basel). 2019 Mar 24;11(3):419. doi: 10.3390/cancers11030419.

Authors

Iordanka A Ivanova^{1

2

3}, Shinthujah Arulanantham^{4

5

6}, Kevin Barr⁷, Mario Cepeda⁸, Katie M Parkins^{9

10}, Amanda M Hamilton^{11

12}, Danielle Johnston¹³, Silvia Penuela^{14

15}, David A Hess^{16

17}, John A Ronald^{18

19}, Lina Dagnino^{20

21

22

23}

Affiliations

¹ Department of Physiology and Pharmacology, University of Western Ontario, London, ON N6A 5C1, Canada. iivanov3@uwo.ca.
² Children's Health Research Institute, University of Western Ontario, London, ON N6C 2V5, Canada. iivanov3@uwo.ca.
³ Lawson Health Research Institute, University of Western Ontario, London, ON N6C 2R5, Canada. iivanov3@uwo.ca.
⁴ Department of Physiology and Pharmacology, University of Western Ontario, London, ON N6A 5C1, Canada. sarulana@uwo.ca.
⁵ Children's Health Research Institute, University of Western Ontario, London, ON N6C 2V5, Canada. sarulana@uwo.ca.
⁶ Lawson Health Research Institute, University of Western Ontario, London, ON N6C 2R5, Canada. sarulana@uwo.ca.
⁷ Department of Physiology and Pharmacology, University of Western Ontario, London, ON N6A 5C1, Canada. kevin.barr@schulich.uwo.ca.
⁸ Department of Urology, Mayo Clinic, Rochester, MN 55902, USA. dr.mcepeda@gmail.com.
⁹ Department of Medical Biophysics, University of Western Ontario, London N6A 5C1, ON N6C 2R5, Canada. kparkin8@uwo.ca.
¹⁰ Robarts Research Institute, University of Western Ontario, London, ON N6A 5B7, Canada. kparkin8@uwo.ca.
¹¹ Department of Medical Biophysics, University of Western Ontario, London N6A 5C1, ON N6C 2R5, Canada. hamilton@robarts.ca.
¹² Robarts Research Institute, University of Western Ontario, London, ON N6A 5B7, Canada. hamilton@robarts.ca.
¹³ Department of Anatomy and Cell Biology, University of Western Ontario, London, ON N6A 5C1, Canada. Danielle.Johnston@schulich.uwo.ca.
¹⁴ Department of Anatomy and Cell Biology, University of Western Ontario, London, ON N6A 5C1, Canada. Silvia.Penuela@schulich.uwo.ca.
¹⁵ Department of Oncology, University of Western Ontario, London, ON N6A 5C1, Canada. Silvia.Penuela@schulich.uwo.ca.
¹⁶ Department of Physiology and Pharmacology, University of Western Ontario, London, ON N6A 5C1, Canada. dhess@robarts.ca.
¹⁷ Robarts Research Institute, University of Western Ontario, London, ON N6A 5B7, Canada. dhess@robarts.ca.
¹⁸ Department of Medical Biophysics, University of Western Ontario, London N6A 5C1, ON N6C 2R5, Canada. jronald@robarts.ca.
¹⁹ Robarts Research Institute, University of Western Ontario, London, ON N6A 5B7, Canada. jronald@robarts.ca.
²⁰ Department of Physiology and Pharmacology, University of Western Ontario, London, ON N6A 5C1, Canada. ldagnino@uwo.ca.
²¹ Children's Health Research Institute, University of Western Ontario, London, ON N6C 2V5, Canada. ldagnino@uwo.ca.
²² Lawson Health Research Institute, University of Western Ontario, London, ON N6C 2R5, Canada. ldagnino@uwo.ca.
²³ Department of Oncology, University of Western Ontario, London, ON N6A 5C1, Canada. ldagnino@uwo.ca.

Abstract

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.

Keywords: FER; metastasis; tumor invasion; tyrosine kinase.

Abstract

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