ArticleScience signaling2020
A PI3K- and GTPase-independent Rac1-mTOR mechanism mediates MET-driven anchorage-independent cell growth but not migration.
Article in Science signaling, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- RAC1 signaling in polyploid giant cancer cells: Implications for tumorigenesis and therapy resistance.Cancer letters · 2026Review
- IQGAP Family Proteins in Colorectal Cancer: Molecular Mechanisms and Prognostic Implications.Diagnostics (Basel, Switzerland) · 2026Review
- The RhoG-Binding Domain of ELMO1 Rescues the PTENopathy-like Phenotype in Oligodendroglial FBD-102b Cells.International journal of molecular sciences · 2026Article
- Transient intracellular expression of PD-L1 and VEGFR2 bispecific nanobody in cancer cells inspires long-term T cell activation and infiltration to combat tumor and inhibit cancer metastasis.Molecular cancer · 2025Article
- Sarcoidosis: molecular mechanisms and therapeutic strategies.Molecular biomedicine · 2025Review
- Biased signaling by mutant EGFR underlies dependence on PKCα in lung adenocarcinoma.Cell reports · 2024Article
- Repurposing Osimertinib and Gedatolisib for Glioblastoma Treatment: Evidence of Synergistic Effects in an In Vitro Phenotypic Study.Pharmaceuticals (Basel, Switzerland) · 2024Article
- [Platelet-specificNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- Mechanisms of drug resistance in nutrient-depleted colorectal cancer cells: insights into lysosomal and mitochondrial drug sequestration.Biology open · 2024Review
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- Ibandronate promotes autophagy by inhibiting Rac1-mTOR signaling pathway in vitro and in vivo.Cell death discovery · 2022Article
- c-Met-integrin cooperation: Mechanisms, tumorigenic effects, and therapeutic relevance.Frontiers in cell and developmental biology · 2022Review
- TIPE2 is a checkpoint of natural killer cell maturation and antitumor immunity.Science advances · 2021Article
- GEFT Inhibits Autophagy and Apoptosis in RhabdomyosarcomaFrontiers in oncology · 2021Article
- Unconventional role of RAC1 in MET-driven anchorage-independent tumor growth.Molecular & cellular oncology · 2020Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Receptor tyrosine kinases (RTKs) are often overexpressed or mutated in cancers and drive tumor growth and metastasis. In the current model of RTK signaling, including that of MET, downstream phosphatidylinositol 3-kinase (PI3K) mediates both cell proliferation and cell migration, whereas the small guanosine triphosphatase (GTPase) Rac1 mediates cell migration. However, in cultured NIH3T3 and glioblastoma cells, we found that class I PI3K mediated oncogenic MET-induced cell migration but not anchorage-independent growth. In contrast, Rac1 regulated both processes in distinct ways. Downstream of PI3K, Rac1 mediated cell migration through its GTPase activity, whereas independently of PI3K, Rac1 mediated anchorage-independent growth in a GTPase-independent manner through an adaptor function. Through its RKR motif, Rac1 formed a complex with the kinase mTOR to promote its translocation to the plasma membrane, where its activity promoted anchorage-independent growth of the cell cultures. Inhibiting mTOR with rapamycin suppressed the growth of subcutaneous MET-mutant cell grafts in mice, including that of MET inhibitor-resistant cells. These findings reveal a GTPase-independent role for Rac1 in mediating a PI3K-independent MET-to-mTOR pathway and suggest alternative or combined strategies that might overcome resistance to RTK inhibitors in patients with cancer.
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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.