ArticleOncogene1999
RalA requirement for v-Src- and v-Ras-induced tumorigenicity and overproduction of urokinase-type plasminogen activator: involvement of metalloproteases.
Article in Oncogene, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 84 citations in OpenAlex.
- FOXD1-dependent RalA-ANXA2-Src complex promotes CTC formation in breast cancer.Journal of experimental & clinical cancer research : CR · 2022Article
- K15 promoter-driven enforced expression of NKIRAS exhibits tumor suppressive activity against the development of DMBA/TPA-induced skin tumors.Scientific reports · 2021Article
- Elevated phospholipase D activity in androgen-insensitive prostate cancer cells promotes both survival and metastatic phenotypes.Cancer letters · 2018Article
- Galectin-8 induces partial epithelial-mesenchymal transition with invasive tumorigenic capabilities involving a FAK/EGFR/proteasome pathway in Madin-Darby canine kidney cells.Molecular biology of the cell · 2018Article
- Hsp90-binding immunophilin FKBP51 forms complexes with hTERT enhancing telomerase activity.Molecular oncology · 2016Article
- Article
- Hypoxia-independent drivers of melanoma angiogenesis.Frontiers in oncology · 2015Review
- Paxillin phosphorylation and complexing with Erk and FAK are regulated by PLD activity in MDA-MB-231 cells.Cellular signalling · 2012Article
- Choline metabolism in malignant transformation.Nature reviews. Cancer · 2011Review
- Suppression of uPA and uPAR blocks radiation-induced MCP-1 mediated recruitment of endothelial cells in meningioma.Cellular signalling · 2011Article
- Reactive oxygen generated by NADPH oxidase 1 (Nox1) contributes to cell invasion by regulating matrix metalloprotease-9 production and cell migration.The Journal of biological chemistry · 2010Article
- Rac1 and Cdc42 are regulators of HRasV12-transformation and angiogenic factors in human fibroblasts.BMC cancer · 2010Article
- Ral overactivation in malignant peripheral nerve sheath tumors.Molecular and cellular biology · 2009Article
- Article
- Mutation of Y179 on phospholipase D2 (PLD2) upregulates DNA synthesis in a PI3K-and Akt-dependent manner.Cellular signalling · 2008Article
- Suppression of cell migration by protein kinase Cdelta.Oncogene · 2005Article
- Ral-GTPases: good chances for a long-lasting fame.Oncogene · 2005Article
- RalA interacts with ZONAB in a cell density-dependent manner and regulates its transcriptional activity.The EMBO journal · 2005Article
- Review
- Differential regulation of cell motility and invasion by FAK.The Journal of cell biology · 2003Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Overproduction of urokinase-type plasminogen activator (uPA) and metalloproteases (MMPs) is strongly correlated with tumorigenicity and with invasive and metastatic phenotypes of human and experimental tumors. We demonstrated previously that overproduction of uPA in tumor cells is mediated by a phospholipase D (PLD)- and protein kinase C-dependent mechanism. The oncogenic stimulus of v-Src and v-Ras results in the activation of PLD, which is dependent upon the monomeric GTPase RalA. We have therefore investigated whether RalA plays a role in uPA and MMP overproduction that is observed in response to oncogenic signals. We report here that NIH3T3 cells transformed by both v-Src and v-Ras, constitutively overproduce uPA and that expression of a dominant negative RalA mutant (S28N) blocks overproduction of uPA in both the v-Src-and v-Ras-transformed cells. v-Src and v-Ras also induced an upregulation of the activity of MMP-2 and MMP-9 as detected by zymograms, however only the v-Src induction correlated with MMP protein levels detected by Western blot analysis. The dominant negative RalA mutant blocked increased MMP-2 and 9 overproduction induced by v-Src, but not the increased activity of MMP-2 and 9 induced by v-Ras. And, consistent with a role for the RalA/PLD pathway in mitogenesis and tumor development, the dominant negative RalA mutant completely blocked tumor formation by v-Src- and v-Ras-transformed NIH3T3 cells injected subcutaneously in syngeneic mice. The data presented here implicate RalA and PLD as signaling mediators for tumor formation and protease production by transformed cells.
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