ArticleThe Journal of cell biology2019
SRC and ERK cooperatively phosphorylate DLC1 and attenuate its Rho-GAP and tumor suppressor functions.
Article in The Journal of cell biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 17 citations in OpenAlex.
- Chromatin accessibility regulates age-dependent nuclear mechanotransduction.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Filamin a binds deleted in liver cancer 1 (DLC1) to promote its tumor suppressor activity and inhibit the SRF coactivator MRTF-A.Neoplasia (New York, N.Y.) · 2026Article
- Mechanosensitive biochemical imprinting of the talin interaction with DLC1 regulates RhoA activity and cardiomyocyte remodeling.Science advances · 2025Article
- The pro-oncogenic noncanonical activity of a RAS•GTP:RanGAP1 complex facilitates nuclear protein export.Nature cancer · 2024Article
- STARD12/14 are diagnostic and prognostic biomarkers of lung adenocarcinoma associated with epigenetic regulation, immune infiltration and ferroptosis.International journal of medical sciences · 2023Article
- Proteasomal turnover of the RhoGAP tumor suppressor DLC1 is regulated by HECTD1 and USP7.Scientific reports · 2022Article
- Inhibition of cytoplasmic EZH2 induces antitumor activity through stabilization of the DLC1 tumor suppressor protein.Nature communications · 2021Article
- The tumor suppressor activity of DLC1 requires the interaction of its START domain with Phosphatidylserine, PLCD1, and Caveolin-1.Molecular cancer · 2021Article
- The Crossroads between RAS and RHO Signaling Pathways in Cellular Transformation, Motility and Contraction.Genes · 2021Review
- DLC1 deficiency and YAP signaling drive endothelial cell contact inhibition of growth and tumorigenesis.Oncogene · 2019Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SRC and ERK kinases control many cell biological processes that promote tumorigenesis by altering the activity of oncogenic and tumor suppressor proteins. We identify here a physiological interaction between DLC1, a focal adhesion protein and tumor suppressor, with SRC and ERK. The tumor suppressor function of DLC1 is attenuated by phosphorylation of tyrosines Y451 and Y701 by SRC, which down-regulates DLC1's tensin-binding and Rho-GAP activities. ERK1/2 phosphorylate DLC1 on serine S129, which increases both the binding of SRC to DLC1 and SRC-dependent phosphorylation of DLC1. SRC inhibitors exhibit potent antitumor activity in a DLC1-positive transgenic cancer model and a DLC1-positive tumor xenograft model, due to reactivation of the tumor suppressor activities of DLC1. Combined treatment of DLC1-positive tumors with SRC plus AKT inhibitors has even greater antitumor activity. Together, these findings indicate cooperation between the SRC, ERK1/2, and AKT kinases to reduce DLC1 Rho-GAP and tumor suppressor activities in cancer cells, which can be reactivated by the kinase inhibitors.
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