ArticleOncogene2017
Tumor suppressor Pdcd4 attenuates Sin1 translation to inhibit invasion in colon carcinoma.
Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 64 citations in OpenAlex.
- Pdcd4-Rictor interaction suppresses mTORC2-PFKFB3 axis and tumorigenesis in NSCLC.Neoplasia (New York, N.Y.) · 2026Article
- Exosomal miR-373-3p Derived from Docetaxel-Resistant Lung Cancer Cells Targets PDCD4 to Promote Proliferation and Inhibit Apoptosis in Lung Cancer Cells.Biomedicines · 2026Article
- Pdcd4-Rictor Interaction Suppresses PFKFB3 to inhibit Tumorigenesis.Research square · 2026Article
- PDCD4: A Double-Edged Sword in Neurological Diseases.Molecular neurobiology · 2026Review
- GLUT3 drives paclitaxel resistance in peritoneal metastatic gastric cancer by promoting H3K18 lactylation-mediated MAPKAP1 transcription to suppress ferroptosis.International journal of biological sciences · 2026Article
- Article
- Mutant NPM1 modulates PDCD4 ubiquitination degradation and facilitates leukemogenesis.iScience · 2025Article
- Translational Inhibition of Slug by Pdcd4 Contributes to Invasion Inhibition in Colorectal Cancer Cells.Cancer medicine · 2025Article
- Phosphorylation of USP33 by CDK1 stabilizes the mTORC2 component SIN1.Cell death & disease · 2025Article
- The kinase PLK1 promotes Hedgehog signaling-dependent resistance to the antiandrogen enzalutamide in metastatic prostate cancer.Science signaling · 2025Article
- Discovery of a sushi domain-containing protein 2-positive phenotype in circulating tumor cells of metastatic breast cancer patients.Scientific reports · 2025Article
- Advances in the study of the relationship betweenFrontiers in cell and developmental biology · 2025Review
- The Impact of Pdcd4, a Translation Inhibitor, on Drug Resistance.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Human tumor suppressor protein Pdcd4 binds at the mRNA entry channel in the 40S small ribosomal subunit.Nature communications · 2024Article
- PDCD4 triggers α-synuclein accumulation and motor deficits via co-suppressing TFE3 and TFEB translation in a model of Parkinson's disease.NPJ Parkinson's disease · 2024Article
- Protein translation: biological processes and therapeutic strategies for human diseases.Signal transduction and targeted therapy · 2024Review
- The mTORC2 signaling network: targets and cross-talks.The Biochemical journal · 2024Review
- Atg7 senses ATP levels and regulates AKTCommunications biology · 2023Article
- Unmasking the tumourigenic role of SIN1/MAPKAP1 in the mTOR complex 2.Clinical and translational medicine · 2023Review
- Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Programmed cell death 4 (Pdcd4), a tumor invasion suppressor, is frequently downregulated in colorectal cancer and other cancers. In this study, we find that loss of Pdcd4 increases the activity of mammalian target of rapamycin complex 2 (mTORC2) and thereby upregulates Snail expression. Examining the components of mTORC2 showed that Pdcd4 knockdown increased the protein but not mRNA level of stress-activated-protein kinase interacting protein 1 (Sin1), which resulted from enhanced Sin1 translation. To understand how Pdcd4 regulates Sin1 translation, the SIN1 5' untranslated region (5'UTR) was fused with luciferase reporter and named as 5'Sin1-Luc. Pdcd4 knockdown/knockout significantly increased the translation of 5'Sin1-Luc but not the control luciferase without the SIN1 5'UTR, suggesting that Sin1 5'UTR is necessary for Pdcd4 to inhibit Sin1 translation. Ectopic expression of wild-type Pdcd4 and Pdcd4(157-469), a deletion mutant that binds to translation initiation factor 4A (eIF4A), sufficiently inhibited Sin1 translation, and thus suppressed mTORC2 kinase activity and invasion in colon tumor cells. By contrast, Pdcd4(157-469)(D253A,D418A), a mutant that does not bind to eIF4A, failed to inhibit Sin1 translation, and consequently failed to repress mTORC2 activity and invasion. In addition, directly inhibiting eIF4A with silvestrol significantly suppressed Sin1 translation and attenuated invasion. These results indicate that Pdcd4-inhibited Sin1 translation is through suppressing eIF4A, and functionally important for suppression of mTORC2 activity and invasion. Moreover, in colorectal cancer tissues, the Sin1 protein but not mRNA was significantly upregulated while Pdcd4 protein was downregulated, suggesting that loss of Pdcd4 might correlate with Sin1 protein level but not mRNA level in colorectal cancer patients. Taken together, our work reveals a novel mechanism by which Pdcd4 inhibits Sin1 translation to attenuatemTORC2 activity and thereby suppresses invasion.
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Registered trials
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