Premium
Lysophosphatidic acid promotes lung carcinoma cell migration via ARHGEF17, a RhoGEF directly controlled by Gβγ
Author(s) -
García Irving
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.02358
Subject(s) - lysophosphatidic acid , cell migration , microbiology and biotechnology , rhoa , pertussis toxin , actin cytoskeleton , rac1 , gtpase , guanine nucleotide exchange factor , chemotaxis , cell , cancer research , biology , chemistry , cytoskeleton , receptor , g protein , signal transduction , biochemistry
Cell migration plays an essential role in multiple physiological processes, such as the immune response. However, this process contributes to pathological situations such as inflammation and metastatic cancer. During cell migration, cells reshape their actin cytoskeleton, a process finely regulated by Rho family GTPases (RhoGTPases). RhoGEFs activate RhoGTPases by promoting the exchange of GDP for GTP. Thus, RhoGEFs represent a crucial point between activation of chemotactic receptors and remodeling of the actin cytoskeleton. In this sense, several RhoGEFs have been characterized as important for cancer cell migration. Here, we demonstrate that RhoGEF‐ARHGEF17 is important for lung carcinoma cell migration stimulated with lysophosphatidic acid (LPA). In addition, pull down experiments, to directly assess GEF activation, demonstrated that ARHGEF17 is stimulated by LPA via Gi (sensitive to pertussis toxin ) and by Gβγ. Mechanistically, Gβγ recruits ARHGEF17 to the plasma membrane and disrupts intramolecular inhibitory interactions. Our results indicate a possible participation of ARHGEF17 in the metastatic dissemination of lung carcinoma cells, a possibility under investigation.