LPA, HGF, and EGF utilize distinct combinations of signaling pathways to promote migration and invasion of MDA-MB-231 breast carcinoma cells

Abstract

BackgroundVarious pathways impinge on the actin-myosin pathway to facilitate cell migration and invasion including members of the Rho family of small GTPases and MAPK. However, the signaling components that are considered important for these processes vary substantially within the literature with certain pathways being favored. These distinctions in signaling pathways utilized are often attributed to differences in cell type or physiological conditions; however, these attributes have not been systematically assessed.MethodsTo address this question, we analyzed the migration and invasion of MDA-MB-231 breast carcinoma cell line in response to various stimuli including lysophosphatidic acid (LPA), hepatocyte growth factor (HGF) and epidermal growth factor (EGF) and determined the involvement of select signaling pathways that impact myosin light chain phosphorylation.ResultsLPA, a potent stimulator of the Rho-ROCK pathway, surprisingly did not require the Rho-ROCK pathway to stimulate migration but instead utilized Rac and MAPK. In contrast, LPA-stimulated invasion required Rho, Rac, and MAPK. Of these three major pathways, EGF-stimulated MDA-MB-231 migration and invasion required Rho; however, Rac was essential only for invasion and MAPK was dispensable for migration. HGF signaling, interestingly, utilized the same pathways for migration and invasion, requiring Rho but not Rac signaling. Notably, the dependency of HGF-stimulated migration and invasion as well as EGF-stimulated invasion on MAPK was subject to the inhibitors used. As expected, myosin light chain kinase (MLCK), a convergence point for MAPK and Rho family GTPase signaling, was required for all six conditions.ConclusionsThese observations suggest that, while multiple signaling pathways contribute to cancer cell motility, not all pathways operate under all conditions. Thus, our study highlights the plasticity of cancer cells to adapt to multiple migratory cues.

The lipid-transfer protein Nir2 enhances epithelial-mesenchymal transition and facilitates breast cancer metastasis

“…The MAPK pathway is also involved in EGF-induced MDA-MB-231 cell migration (Harrison et al, 2013). We, therefore, examined the influence of Nir2 depletion on these signaling cascades.…”

Gα13/PDZ-RhoGEF/RhoA Signaling Is Essential for Gastrin-Releasing Peptide Receptor–Mediated Colon Cancer Cell Migration

“…These studies have identified that PRG-RhoA-ROCK signaling regulates cell migration through induction of adhesion complexes and spatial regulation of actinomyosin contractile machinery (Iwanicki et al, 2008;Struckhoff et al, 2013). Prior work has also demonstrated that growth factor receptor tyrosine kinases also use Rho-ROCK signaling to promote tumor cell migration and invasion (Somlyo et al, 2000;Harrison et al, 2013). Hence, it is clear that ROCK can be an ideal molecular target for prevention of tumor cell migration and metastasis.…”

Varying effects of EGF, HGF and TGFβ on formation of invadopodia and invasiveness of melanoma cell lines of different origin

“…Vast of signaling pathways have varying effects on actin cytoskeleton 42 and different external stimuli trigger diverse intracellular signaling pathways having impact on cells’ motility. 43 On the other hand EGF was shown to trigger dismantle of focal adhesions, what leaded to lowered adhesion of the cells and thus increased cells’ motility 44,45 and decreased adhesion favors ameboid-like mode of motility. 39,46 Triggering of divergent motility modes in melanoma cells by tested here SMs should be further studied.…”