RKIP regulates differentiation-related features in melanocytic cells

Penas C, Apraiz A, Muñoa I, Arroyo-Berdugo Y, Rasero J, Ezkurra PA, Velasco V, Subiran N, Boßerhoff AK, Alonso S, Asumendi A, Boyano MD (2020)

Publication Type: Journal article

Publication year: 2020

Journal

Cancers MDPI

Book Volume: 12

Pages Range: 1-22

Article Number: 1451

Journal Issue: 6

DOI: 10.3390/cancers12061451

Abstract

Raf Kinase Inhibitor Protein (RKIP) has been extensively reported as an inhibitor of key signaling pathways involved in the aggressive tumor phenotype and shows decreased expression in several types of cancers. However, little is known about RKIP in melanoma or regarding its function in normal cells. We examined the role of RKIP in both primary melanocytes and malignant melanoma cells and evaluated its diagnostic and prognostic value. IHC analysis revealed a significantly higher expression of RKIP in nevi compared with early-stage (stage I–II, AJCC 8th) melanoma biopsies. Proliferation, wound healing, and collagen-coated transwell assays uncovered the implication of RKIP on the motility but not on the proliferative capacity of melanoma cells as RKIP protein levels were inversely correlated with the migration capacity of both primary and metastatic melanoma cells but did not alter other parameters. As shown by RNA sequencing, endogenous RKIP knockdown in primary melanocytes triggered the deregulation of cellular differentiation-related processes, including genes (i.e., ZEB1, THY-1) closely related to the EMT. Interestingly, NANOG was identified as a putative transcriptional regulator of many of the deregulated genes, and RKIP was able to decrease the activation of the NANOG promoter. As a whole, our data support the utility of RKIP as a diagnostic marker for early-stage melanomas. In addition, these findings indicate its participation in the maintenance of a differentiated state of melanocytic cells by modulating genes intimately linked to the cellular motility and explain the progressive decrease of RKIP often described in tumors.

Authors with CRIS profile

Anja Katrin Boßerhoff Lehrstuhl für Biochemie und Molekulare Medizin

Involved external institutions

University of Basque Country / Universidad del Pais Vasco (UPV) / Euskal Herriko Unibersitatea (EHU) ES Spain (ES) Biocruces Health Research Institute ES Spain (ES)

How to cite

APA:

Penas, C., Apraiz, A., Muñoa, I., Arroyo-Berdugo, Y., Rasero, J., Ezkurra, P.A.,... Boyano, M.D. (2020). RKIP regulates differentiation-related features in melanocytic cells. Cancers, 12(6), 1-22. https://dx.doi.org/10.3390/cancers12061451

MLA:

Penas, Cristina, et al. "RKIP regulates differentiation-related features in melanocytic cells." Cancers 12.6 (2020): 1-22.

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