The rise of T-type channels in melanoma progression and chemotherapeutic resistance

Lía Alza; Anna Visa; Judit Herreros; Carles Cantí

doi:10.1016/j.bbcan.2020.188364

The rise of T-type channels in melanoma progression and chemotherapeutic resistance

Biochim Biophys Acta Rev Cancer. 2020 Apr;1873(2):188364. doi: 10.1016/j.bbcan.2020.188364. Epub 2020 Apr 7.

Authors

Lía Alza¹, Anna Visa¹, Judit Herreros¹, Carles Cantí²

Affiliations

¹ Universitat de Lleida-IRBlLeida, Cell Calcium Signaling Lab, 25198, Rovira Roure, 80, Lleida, Spain.
² Universitat de Lleida-IRBlLeida, Cell Calcium Signaling Lab, 25198, Rovira Roure, 80, Lleida, Spain. Electronic address: [email protected].

PMID: 32275934
DOI: 10.1016/j.bbcan.2020.188364

Abstract

Hyperactivation of the Mitogen Activated Protein Kinase (MAPK) pathway is prevalent in melanoma, principally due to mutations in the BRAF and NRAS genes. MAPK inhibitors are effective only short-term, and recurrence occurs due to functional redundancies or intertwined pathways. The remodeling of Ca²⁺ signaling is also common in melanoma cells, partly through the increased expression of T-type channels (TTCCs). Here we summarize current knowledge about the prognostic value and molecular targeting of TTCCs. Furthermore, we discuss recent evidence pointing to TTCCs as molecular switches for melanoma chemoresistance, which set the grounds for novel combined therapies against the advanced disease.

Keywords: Chemotherapeutic resistance; MAPK; Macroautophagy; Melanoma; PTEN mutants; RAF/RAS mutants; T-type channels.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Antineoplastic Agents / pharmacology
Antineoplastic Agents / therapeutic use*
Calcium Channel Blockers / pharmacology
Calcium Channel Blockers / therapeutic use
Calcium Channels, T-Type / metabolism*
Cell Line, Tumor
Disease Progression
Drug Resistance, Neoplasm / drug effects
Drug Resistance, Neoplasm / genetics
GTP Phosphohydrolases / antagonists & inhibitors
GTP Phosphohydrolases / genetics
Humans
Kaplan-Meier Estimate
MAP Kinase Signaling System / drug effects*
MAP Kinase Signaling System / genetics
Melanoma / drug therapy*
Melanoma / genetics
Melanoma / mortality
Melanoma / pathology
Membrane Proteins / antagonists & inhibitors
Membrane Proteins / genetics
Mutation
Prognosis
Protein Kinase Inhibitors / pharmacology
Protein Kinase Inhibitors / therapeutic use
Proto-Oncogene Proteins B-raf / antagonists & inhibitors
Proto-Oncogene Proteins B-raf / genetics
Skin Neoplasms / drug therapy*
Skin Neoplasms / genetics
Skin Neoplasms / mortality
Skin Neoplasms / pathology
Treatment Outcome

Substances

Antineoplastic Agents
Calcium Channel Blockers
Calcium Channels, T-Type
Membrane Proteins
Protein Kinase Inhibitors
BRAF protein, human
Proto-Oncogene Proteins B-raf
GTP Phosphohydrolases
NRAS protein, human