Rac-GEF/Rac Signaling and Metastatic Dissemination in Lung Cancer.
Rac
Rac-GEF
adenocarcinoma
lung cancer
metastasis
tumorigenesis
Journal
Frontiers in cell and developmental biology
ISSN: 2296-634X
Titre abrégé: Front Cell Dev Biol
Pays: Switzerland
ID NLM: 101630250
Informations de publication
Date de publication:
2020
2020
Historique:
received:
03
01
2020
accepted:
11
02
2020
entrez:
12
3
2020
pubmed:
12
3
2020
medline:
12
3
2020
Statut:
epublish
Résumé
Lung cancer is the leading cause of cancer-related deaths worldwide, with non-small cell lung cancer (NSCLC) representing ∼85% of new diagnoses. The disease is often detected in an advanced metastatic stage, with poor prognosis and clinical outcome. In order to escape from the primary tumor, cancer cells acquire highly motile and invasive phenotypes that involve the dynamic reorganization of the actin cytoskeleton. These processes are tightly regulated by Rac1, a small G-protein that participates in the formation of actin-rich membrane protrusions required for cancer cell motility and for the secretion of extracellular matrix (ECM)-degrading proteases. In this perspective article we focus on the mechanisms leading to aberrant Rac1 signaling in NSCLC progression and metastasis, highlighting the role of Rac Guanine nucleotide Exchange Factors (GEFs). A plausible scenario is that specific Rac-GEFs activate discrete intracellular pools of Rac1, leading to unique functional responses in the context of specific oncogenic drivers, such as mutant EGFR or mutant KRAS. The identification of dysregulated Rac signaling regulators may serve to predict critical biomarkers for metastatic disease in lung cancer patients, ultimately aiding in refining patient prognosis and decision-making in the clinical setting.
Identifiants
pubmed: 32158759
doi: 10.3389/fcell.2020.00118
pmc: PMC7051914
doi:
Types de publication
Journal Article
Langues
eng
Pagination
118Subventions
Organisme : NIEHS NIH HHS
ID : P30 ES013508
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA189765
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA196232
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES026023
Pays : United States
Informations de copyright
Copyright © 2020 Cooke, Baker and Kazanietz.
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