ArticleMolecular biology of the cell2005
Protein kinase A gating of a pseudopodial-located RhoA/ROCK/p38/NHE1 signal module regulates invasion in breast cancer cell lines.
Article in Molecular biology of the cell, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 95 citations in OpenAlex.
- Genetic Variants in Caveolin-1 and RhoA/ROCK1 Are Associated with Clear Cell Renal Cell Carcinoma Risk in a Chinese Population.PloS one · 2015Trial
- A PI3Kγ mimetic peptide triggers CFTR gating, bronchodilation, and reduced inflammation in obstructive airway diseases.Science translational medicine · 2022Article
- Rho-GEF Trio regulates osteosarcoma progression and osteogenic differentiation through Rac1 and RhoA.Cell death & disease · 2021Article
- Pathway-Based Personalized Analysis of Pan-Cancer Transcriptomic Data.Biomedicines · 2021Article
- Recent progress in developing fluorescent probes for imaging cell metabolites.Biomedical materials (Bristol, England) · 2021Review
- Integrin-Linked Kinase Links Integrin Activation to Invadopodia Function and Invasion via the p(T567)-Ezrin/NHERF1/NHE1 Pathway.International journal of molecular sciences · 2021Article
- Na/H exchanger NHE1 acts upstream of rho GTPases to promote neurite outgrowth.Journal of cell communication and signaling · 2020Article
- The impact of tumour pH on cancer progression: strategies for clinical intervention.Exploration of targeted anti-tumor therapy · 2020Review
- LncRNA AFAP1-AS1 promotes tumorigenesis and epithelial-mesenchymal transition of osteosarcoma through RhoC/ROCK1/p38MAPK/Twist1 signaling pathway.Journal of experimental & clinical cancer research : CR · 2019Article
- Hunt for the tipping point during endocrine resistance process in breast cancer by dynamic network biomarkers.Journal of molecular cell biology · 2019Article
- Structural and Functional Changes in the NaInternational journal of molecular sciences · 2019Review
- NRP-1 interacts with GIPC1 and SYX to activate p38 MAPK signaling and cancer stem cell survival.Molecular carcinogenesis · 2019Article
- Interrogating cyclic AMP signaling using optical approaches.Cell calcium · 2017Review
- Role of Rho kinase and Na+/H+ exchange in hypoxia-induced pulmonary arterial smooth muscle cell proliferation and migration.Physiological reports · 2016Article
- Overexpression of CD61 promotes hUC-MSC differentiation into male germ-like cells.Cell proliferation · 2016Article
- The role of semaphorin 4D in tumor development and angiogenesis in human breast cancer.OncoTargets and therapy · 2016Article
- Na(+)/H(+) exchange and hypoxic pulmonary hypertension.Pulmonary circulation · 2015Review
- Thrombospondin-1 repression is mediated via distinct mechanisms in fibroblasts and epithelial cells.Oncogene · 2015Article
- Expression of ezrin, CD44, and VEGF in giant cell tumor of bone and its significance.World journal of surgical oncology · 2015Article
- RhoA Kinase (Rock) and p90 Ribosomal S6 Kinase (p90Rsk) phosphorylation of the sodium hydrogen exchanger (NHE1) is required for lysophosphatidic acid-induced transport, cytoskeletal organization and migration.Cellular signalling · 2015Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Metastasis results from a sequence of selective events often involving interactions with elements of the tumor-specific physiological microenvironment. The low-serum component of this microenvironment confers increased motility and invasion in breast cancer cells by activating the Na+/H+ exchanger isoform 1 (NHE1). The present study was undertaken to characterize the signal transduction mechanisms underlying this serum deprivation-dependent activation of both the NHE1 and the concomitant invasive characteristics such as leading edge pseudopodia development and penetration of matrigel in breast cancer cell lines representing different stages of metastatic progression. Using pharmacological and genetic manipulation together with transport and kinase activity assays, we observe that the activation of the NHE1 and subsequent invasion by serum deprivation in metastatic human breast cells is coordinated by a sequential RhoA/p160ROCK/p38MAPK signaling pathway gated by direct protein kinase A phosphorylation and inhibition of RhoA. Fluorescence resonance energy transfer imaging of RhoA activity and immunofluorescence analysis of phospho-RhoA and NHE1 show that serum deprivation dynamically remodels the cell, forming long, leading edge pseudopodia and that this signal module is preferentially compartmentalized in these leading edge pseudopodia, suggesting a tight topographic relation of the signaling module to an invasion-specific cell structure.
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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.