ArticleJournal of cell science2013
PDZ-RhoGEF is essential for CXCR4-driven breast tumor cell motility through spatial regulation of RhoA.
Article in Journal of cell science, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 41 citations in OpenAlex.
- Reciprocal regulation of Solo and Src orchestrates Src trafficking to promote mesenchymal cell migration.iScience · 2025Article
- Optogenetic control of a GEF of RhoA uncovers a signaling switch from retraction to protrusion.eLife · 2025Article
- A network of GαScience signaling · 2022Article
- GPCRs thatSmall GTPases · 2022Review
- Dysfunction of Trio GEF1 involves in excitatory/inhibitory imbalance and autism-like behaviors through regulation of interneuron migration.Molecular psychiatry · 2021Article
- 5-Hydroxymethylcytosine profiles of cfDNA are highly predictive of R-CHOP treatment response in diffuse large B cell lymphoma patients.Clinical epigenetics · 2021Article
- The RGS-RhoGEFs control the amplitude of YAP1 activation by serum.Scientific reports · 2021Article
- Article
- Characterization of BRCA1-deficient premalignant tissues and cancers identifies Plekha5 as a tumor metastasis suppressor.Nature communications · 2020Article
- Systems analysis of RhoGEF and RhoGAP regulatory proteins reveals spatially organized RAC1 signalling from integrin adhesions.Nature cell biology · 2020Article
- Migration rather than proliferation transcriptomic signatures are strongly associated with breast cancer patient survival.Scientific reports · 2019Article
- The CXCR4-LASP1-eIF4F Axis Promotes Translation of Oncogenic Proteins in Triple-Negative Breast Cancer Cells.Frontiers in oncology · 2019Article
- PDZ-RhoGEF Is a Signaling Effector for TROY-Induced Glioblastoma Cell Invasion and Survival.Neoplasia (New York, N.Y.) · 2018Article
- Agonist-induced CXCR4 and CB2 Heterodimerization Inhibits Gα13/RhoA-mediated Migration.Molecular cancer research : MCR · 2018Article
- Myosin II-interacting guanine nucleotide exchange factor promotes bleb retraction via stimulating cortex reassembly at the bleb membrane.Molecular biology of the cell · 2018Article
- Carcinoma associated fibroblasts (CAFs) promote breast cancer motility by suppressing mammalian Diaphanous-related formin-2 (mDia2).PloS one · 2018Article
- mDia2 and CXCL12/CXCR4 chemokine signaling intersect to drive tumor cell amoeboid morphological transitions.Biochemical and biophysical research communications · 2017Article
- Endothelin A receptor drives invadopodia function and cell motility through the β-arrestin/PDZ-RhoGEF pathway in ovarian carcinoma.Oncogene · 2016Article
- Rho GEFs and GAPs: emerging integrators of extracellular matrix signaling.Small GTPases · 2015Article
- Gα13/PDZ-RhoGEF/RhoA signaling is essential for gastrin-releasing peptide receptor-mediated colon cancer cell migration.Molecular pharmacology · 2014Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
The CXCL12-CXCR4 chemokine signaling pathway is a well-established driver of cancer progression. One key process promoted by CXCR4 stimulation is tumor cell motility; however, the specific signaling pathways leading to migration remain poorly understood. Previously, we have shown that CXCL12 stimulation of migration depends on temporal regulation of RhoA. However, the specific RhoGEF that translates CXCR4 signaling into RhoA activity and cell motility is unknown. We screened the three regulator of G-protein signaling RhoGEFs (LSC, LARG and PRG) and found that PRG selectively regulated the migration and invasion of CXCR4-overexpressing breast tumor cells. Interestingly, we found that PDZ-RhoGEF (PRG) was required for spatial organization of F-actin structures in the center, but not periphery of the cells. The effects on the cytoskeleton were mirrored by the spatial effects on RhoA activity that were dependent upon PRG. Loss of PRG also enhanced adherens junctions in the epithelial-like MCF7-CXCR4 cell line, and inhibited directional persistence and polarity in the more mesenchymal MDA-MB-231 cell line. Thus, PRG is essential for CXCR4-driven tumor cell migration through spatial regulation of RhoA and the subsequent organization of the cytoskeletal structures that support motility. Furthermore, immunohistochemical analysis of human breast tumor tissues shows a significant increase of PRG expression in the invasive areas of the tumors, suggesting that this RhoGEF is associated with breast tumor invasion in vivo.
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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.