PMID- 32503139
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 12
IP  - 6
DP  - 2020 Jun 3
TI  - RKIP Regulates Differentiation-Related Features in Melanocytic Cells.
LID - 10.3390/cancers12061451 [doi]
LID - 1451
AB  - 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.
FAU - Penas, Cristina
AU  - Penas C
AD  - Department of Cell Biology and Histology, Faculty of Medicine and Nursing, 
      UPV/EHU, 48940 Leioa, Spain.
FAU - Apraiz, Aintzane
AU  - Apraiz A
AUID- ORCID: 0000-0003-1620-9987
AD  - Department of Cell Biology and Histology, Faculty of Medicine and Nursing, 
      UPV/EHU, 48940 Leioa, Spain.
AD  - Biocruces Bizkaia Health Research Institute, 48903 Barakaldo, Spain.
FAU - Munoa, Iraia
AU  - Munoa I
AD  - Biocruces Bizkaia Health Research Institute, 48903 Barakaldo, Spain.
AD  - Department of Physiology, Faculty of Medicine and Nursing, UPV/EHU, 48940 Leioa, 
      Spain.
FAU - Arroyo-Berdugo, Yoana
AU  - Arroyo-Berdugo Y
AD  - Department of Cell Biology and Histology, Faculty of Medicine and Nursing, 
      UPV/EHU, 48940 Leioa, Spain.
FAU - Rasero, Javier
AU  - Rasero J
AD  - Biocruces Bizkaia Health Research Institute, 48903 Barakaldo, Spain.
AD  - Department of Psychology, Carnegie Mellon University, Pittsburg, PA 15213, USA.
FAU - Ezkurra, Pilar A
AU  - Ezkurra PA
AD  - Department of Cell Biology and Histology, Faculty of Medicine and Nursing, 
      UPV/EHU, 48940 Leioa, Spain.
FAU - Velasco, Veronica
AU  - Velasco V
AD  - Biocruces Bizkaia Health Research Institute, 48903 Barakaldo, Spain.
FAU - Subiran, Nerea
AU  - Subiran N
AD  - Biocruces Bizkaia Health Research Institute, 48903 Barakaldo, Spain.
AD  - Department of Physiology, Faculty of Medicine and Nursing, UPV/EHU, 48940 Leioa, 
      Spain.
FAU - Bosserhoff, Anja K
AU  - Bosserhoff AK
AUID- ORCID: 0000-0001-8147-394X
AD  - Institute of Biochemistry, Friedrich-Alexander University of Erlangen-Nurnberg, 
      91054 Erlangen, Germany.
AD  - Comprehensive Cancer Center (CCC) Erlangen-EMN, 91054 Erlangen, Germany.
FAU - Alonso, Santos
AU  - Alonso S
AUID- ORCID: 0000-0003-0221-4048
AD  - Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of 
      Science and Technology, UPV/EHU, 48940 Leioa, Spain.
FAU - Asumendi, Aintzane
AU  - Asumendi A
AUID- ORCID: 0000-0002-2156-2323
AD  - Department of Cell Biology and Histology, Faculty of Medicine and Nursing, 
      UPV/EHU, 48940 Leioa, Spain.
AD  - Biocruces Bizkaia Health Research Institute, 48903 Barakaldo, Spain.
FAU - Boyano, Maria D
AU  - Boyano MD
AD  - Department of Cell Biology and Histology, Faculty of Medicine and Nursing, 
      UPV/EHU, 48940 Leioa, Spain.
AD  - Biocruces Bizkaia Health Research Institute, 48903 Barakaldo, Spain.
LA  - eng
PT  - Journal Article
DEP - 20200603
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC7352799
OTO - NOTNLM
OT  - RKIP
OT  - biomarker
OT  - cell motility
OT  - differentiation
OT  - melanocytes
OT  - melanoma
OT  - transcriptome analysis
COIS- The authors declare no conflict of interest.
EDAT- 2020/06/07 06:00
MHDA- 2020/06/07 06:01
PMCR- 2020/06/03
CRDT- 2020/06/07 06:00
PHST- 2020/05/11 00:00 [received]
PHST- 2020/05/29 00:00 [revised]
PHST- 2020/05/30 00:00 [accepted]
PHST- 2020/06/07 06:00 [entrez]
PHST- 2020/06/07 06:00 [pubmed]
PHST- 2020/06/07 06:01 [medline]
PHST- 2020/06/03 00:00 [pmc-release]
AID - cancers12061451 [pii]
AID - cancers-12-01451 [pii]
AID - 10.3390/cancers12061451 [doi]
PST - epublish
SO  - Cancers (Basel). 2020 Jun 3;12(6):1451. doi: 10.3390/cancers12061451.