ArticleAmerican journal of physiology. Cell physiology2012
Integrin α6β4 cooperates with LPA signaling to stimulate Rac through AKAP-Lbc-mediated RhoA activation.
Article in American journal of physiology. Cell physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 37 citations in OpenAlex.
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- Integrin α6β4 requires plectin and vimentin for adhesion complex distribution and invasive growth.Journal of cell science · 2022Article
- GPCRs thatSmall GTPases · 2022Review
- Rac1-mediated sustained β4 integrin level develops reattachment ability of breast cancer cells after anchorage loss.Cancer science · 2021Article
- Exosome-derived ENO1 regulates integrin α6β4 expression and promotes hepatocellular carcinoma growth and metastasis.Cell death & disease · 2020Article
- PLA2G16 is a mutant p53/KLF5 transcriptional target and promotes glycolysis of pancreatic cancer.Journal of cellular and molecular medicine · 2020Article
- MDA-9/Syntenin (SDCBP): Novel gene and therapeutic target for cancer metastasis.Pharmacological research · 2020Review
- Regulation of neuroblastoma migration, invasion, and in vivo metastasis by genetic and pharmacological manipulation of MDA-9/Syntenin.Oncogene · 2019Article
- Ping-Pong-Tumor and Host in Pancreatic Cancer Progression.Frontiers in oncology · 2019Review
- Article
- αAmerican journal of respiratory cell and molecular biology · 2017Article
- MUC5AC interactions with integrin β4 enhances the migration of lung cancer cells through FAK signaling.Oncogene · 2016Article
- Pancreatic cancer stem cell markers and exosomes - the incentive push.World journal of gastroenterology · 2016Review
- Selection and Characterization of an α6β4 Integrin blocking DNA Aptamer.Molecular therapy. Nucleic acids · 2016Article
- Determination of cell uptake pathways for tumor inhibitor lysyl oxidase propeptide.Molecular oncology · 2016Article
- Integrin α6β4 Promotes Autocrine Epidermal Growth Factor Receptor (EGFR) Signaling to Stimulate Migration and Invasion toward Hepatocyte Growth Factor (HGF).The Journal of biological chemistry · 2015Article
- Clinical significance of the integrin α6β4 in human malignancies.Laboratory investigation; a journal of technical methods and pathology · 2015Review
- Dual functions of NME1 in suppression of cell motility and enhancement of genomic stability in melanoma.Naunyn-Schmiedeberg's archives of pharmacology · 2015Article
- Cytoplasmic domain interactions of syndecan-1 and syndecan-4 with α6β4 integrin mediate human epidermal growth factor receptor (HER1 and HER2)-dependent motility and survival.The Journal of biological chemistry · 2014Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The α(6)β(4) integrin promotes carcinoma invasion through its ability to promote directed migration and polarization of carcinoma cells. In this study, we explore how the α(6)β(4) integrin cooperates with lysophosphatidic acid (LPA) to activate Rho and Rac small GTPases. Through the use of dominant negative Rho constructs, C3 exotransferase, and Rho kinase inhibitor, we find that Rho is critical for LPA-dependent chemotaxis and lamellae formation. However, utilization of specific Rho isoforms depends on integrin α(6)β(4) expression status. Integrin α(6)β(4)-negative MDA-MB-435 cells utilize only RhoC for motility, whereas integrin α(6)β(4)-expressing cells utilize RhoC but additionally activate and utilize RhoA for LPA-dependent cell motility and lamellae formation. Notably, the activation of RhoA by cooperative LPA and integrin α(6)β(4) signaling requires the Rho guanine nucleotide exchange factor AKAP-Lbc. We also determine that integrin α(6)β(4) cannot activate Rac1 directly but promotes LPA-mediated Rac1 activation that is dependent on RhoA activity and de novo β(1) integrin ligation. Finally, we find that the regulation of Rac1 and RhoA in response to LPA is differentially regulated by phosphodiesterases, PKA, and phosphatidylinositol 3-kinase, thus supporting their spatially distinct compartmentalization. In summary, signaling from integrin α(6)β(4) facilitates LPA-stimulated chemotaxis through preferential activation of RhoA, which, in turn, facilitates activation of Rac1.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.