ArticleClinical cancer research : an official journal of the American Association for Cancer Research2012
Ran is a potential therapeutic target for cancer cells with molecular changes associated with activation of the PI3K/Akt/mTORC1 and Ras/MEK/ERK pathways.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 6 citations in OpenAlex.
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- A new candidate oncogenic lncRNA derived from pseudogene WFDC21P promotes tumor progression in gastric cancer.Cell death & disease · 2021Article
- RASSF9 promotes NSCLC cell proliferation by activating the MEK/ERK axis.Cell death discovery · 2021Article
- GEF-independent Ran activation shifts a fraction of the protein to the cytoplasm and promotes cell proliferation.Molecular biomedicine · 2020Article
- Nanoparticulate RNA delivery systems in cancer.Cancer reports (Hoboken, N.J.) · 2020Review
- Osteopontin level and promoter polymorphism in patients with metastatic breast cancer.Current oncology (Toronto, Ont.) · 2020Article
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- XPO1-dependent nuclear export as a target for cancer therapy.Journal of hematology & oncology · 2020Review
- Silencing of PTEN inhibits the oxidative stress damage and hippocampal cell apoptosis induced by Sevoflurane through activating MEK1/ERK signaling pathway in infant rats.Cell cycle (Georgetown, Tex.) · 2020Article
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Authors and funding
12 authors at 4 institutions in 4 countries.
Funding
Abstract
purposeCancer cells have been shown to be more susceptible to Ran knockdown than normal cells. We now investigate whether Ran is a potential therapeutic target of cancers with frequently found mutations that lead to higher Ras/MEK/ERK [mitogen-activated protein/extracellular signal-regulated kinase (ERK; MEK)] and phosphoinositide 3-kinase (PI3K)/Akt/mTORC1 activities. EXPERIMENTAL
designApoptosis was measured by flow cytometry [propidium iodide (PI) and Annexin V staining] and MTT assay in cancer cells grown under different conditions after knockdown of Ran. The correlations between Ran expression and patient survival were examined in breast and lung cancers.
resultsCancer cells with their PI3K/Akt/mTORC1 and Ras/MEK/ERK pathways inhibited are less susceptible to Ran silencing-induced apoptosis. K-Ras-mutated, c-Met-amplified, and Pten-deleted cancer cells are also more susceptible to Ran silencing-induced apoptosis than their wild-type counterparts and this effect is reduced by inhibitors of the PI3K/Akt/mTORC1 and MEK/ERK pathways. Overexpression of Ran in clinical specimens is significantly associated with poor patient outcome in both breast and lung cancers. This association is dramatically enhanced in cancers with increased c-Met or osteopontin expression, or with oncogenic mutations of K-Ras or PIK3CA, all of which are mutations that potentially correlate with activation of the PI3K/Akt/mTORC1 and/or Ras/MEK/ERK pathways. Silencing Ran also results in dysregulation of nucleocytoplasmic transport of transcription factors and downregulation of Mcl-1 expression, at the transcriptional level, which are reversed by inhibitors of the PI3K/Akt/mTORC1 and MEK/ERK pathways.
conclusionRan is a potential therapeutic target for treatment of cancers with mutations/changes of expression in protooncogenes that lead to activation of the PI3K/Akt/mTORC1 and Ras/MEK/ERK pathways.
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