ArticleMolecular and cellular biology2001
Oncogenic Ras blocks anoikis by activation of a novel effector pathway independent of phosphatidylinositol 3-kinase.
Article in Molecular and cellular biology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 115 citations in OpenAlex.
- Accumulation of annexin A2 and S100A10 prevents apoptosis of apically delaminated, transformed epithelial cells.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Structural mechanism for inhibition of PP2A-B56α and oncogenicity by CIP2A.Nature communications · 2023Article
- Distinct metabolic preference of atypical KRAS mutant.Annals of translational medicine · 2020Article
- Article
- CD2AP links actin to PI3 kinase activity to extend epithelial cell height and constrain cell area.The Journal of cell biology · 2020Article
- Atypical KRASCancer discovery · 2020Article
- Pituitary somatolactotropes evade an oncogenic response to Ras.Molecular and cellular endocrinology · 2018Article
- The Balance of PI3K and ERK Signaling Is Dysregulated in Prolactinoma and Modulated by Dopamine.Endocrinology · 2018Article
- R-Ras1 and R-Ras2 Are Essential for Oligodendrocyte Differentiation and Survival for Correct Myelination in the Central Nervous System.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- HOP expression is regulated by p53 and RAS and characteristic of a cancer gene signature.Cell stress & chaperones · 2017Article
- Oncogenic Ras differentially regulates metabolism and anoikis in extracellular matrix-detached cells.Cell death and differentiation · 2016Article
- Article
- PDGF beta targeting in cervical cancer cells suggest a fine-tuning of compensatory signalling pathways to sustain tumourigenic stimulation.Journal of cellular and molecular medicine · 2015Article
- Caveolin-1 regulates metastatic behaviors of anoikis resistant lung cancer cells.Molecular and cellular biochemistry · 2015Article
- Active contractility at E-cadherin junctions and its implications for cell extrusion in cancer.Cell cycle (Georgetown, Tex.) · 2015Article
- A Rab10:RalA G protein cascade regulates insulin-stimulated glucose uptake in adipocytes.Molecular biology of the cell · 2014Article
- Cancer cell survival during detachment from the ECM: multiple barriers to tumour progression.Nature reviews. Cancer · 2014Review
- AEG-1 promotes anoikis resistance and orientation chemotaxis in hepatocellular carcinoma cells.PloS one · 2014Article
- Regulation of Hippo signaling by EGFR-MAPK signaling through Ajuba family proteins.Developmental cell · 2013Article
- The tumor suppressor DiRas3 forms a complex with H-Ras and C-RAF proteins and regulates localization, dimerization, and kinase activity of C-RAF.The Journal of biological chemistry · 2012Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Activated Ras, but not Raf, causes transformation of RIE-1 rat intestinal epithelial cells, demonstrating the importance of Raf-independent effector signaling in mediating Ras transformation. To further assess the contribution of Raf-dependent and Raf-independent function in oncogenic Ras transformation, we evaluated the mechanism by which oncogenic Ras blocks suspension-induced apoptosis, or anoikis, of RIE-1 cells. We determined that oncogenic versions of H-, K-, and N-Ras, as well as the Ras-related proteins TC21 and R-Ras, protected RIE-1 cells from anoikis. Surprisingly, our analyses of Ras effector domain mutants or constitutively activated effectors indicated that activation of Raf-1, phosphatidylinositol 3-kinase (PI3K), or RalGDS alone is not sufficient to promote Ras inhibition of anoikis. Treatment of Ras-transformed cells with the U0126 MEK inhibitor caused partial reversion to an anoikis-sensitive state, indicating that extracellular signal-regulated kinase activation contributes to inhibition of anoikis. Unexpectedly, oncogenic Ras failed to activate Akt, and treatment of Ras-transformed RIE-1 cells with the LY294002 PI3K inhibitor did not affect anoikis resistance or growth in soft agar. Thus, while important for Ras transformation of fibroblasts, PI3K may not be involved in Ras transformation of RIE-1 cells. Finally, inhibition of epidermal growth factor receptor kinase activity did not overcome Ras inhibition of anoikis, indicating that this autocrine loop essential for transformation is not involved in anoikis protection. We conclude that a PI3K- and RalGEF-independent Ras effector(s) likely cooperates with Raf to confer anoikis resistance upon RIE-1 cells, thus underscoring the complex nature by which Ras transforms cells.
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