ArticleCancer research2011
Phosphorylation of serine 68 of Twist1 by MAPKs stabilizes Twist1 protein and promotes breast cancer cell invasiveness.
Article in Cancer research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 162 papers.
What it found
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Who cites it
162 citing papers in PubMed, 234 citations in OpenAlex.
- Loss of Twist impairs tentacle development and induces epithelial neoplasia in the sea anemone Nematostella vectensis.Development (Cambridge, England) · 2026Article
- Adaptive epithelial-mesenchymal bi-directional transition: A key invasive plasticity for tumor metastasis.iScience · 2026Review
- Twist1 overexpression models an aggressive subtype of pancreatic ductal adenocarcinoma in vivo.Lab animal · 2026Article
- Emetine dihydrochloride suppresses the invasiveness and motility of hepatocellular carcinoma cells through MAPK pathway inhibition and Twist1 protein destabilization.Scientific reports · 2026Article
- Generation and Characterization of Twist1 Acetyl-Mimic and Acetyl-Deficient Mouse Models.Genesis (New York, N.Y. : 2000) · 2026Article
- Tumour necrosis factor receptor-associated factor 7 drives leukaemogenesis through the TWIST1-P2RX1-CaJournal of translational medicine · 2026Article
- Detection of Circulating Tumor Cells with an Epithelial-to-Mesenchymal Transition Phenotype.Methods in molecular biology (Clifton, N.J.) · 2026Article
- UCHL1 stabilizes Twist1 via K11/K63-linked deubiquitination to drive tumor metastasis in non-small cell lung cancer.Cell death discovery · 2025Article
- Transcriptional and post-translational mechanisms of ECM remodeling in rotator cuff tendons under hyperlipidemic conditions.Life sciences · 2025Article
- Reciprocal Modulation of Tumour and Immune Cell Motility: Uncovering Dynamic Interplays and Therapeutic Approaches.Cancers · 2025Review
- Roles of Post-Translational Modifications of Transcription Factors Involved in Breast Cancer Hypoxia.Molecules (Basel, Switzerland) · 2025Review
- Crosstalk between lipid metabolism and EMT: emerging mechanisms and cancer therapy.Molecular and cellular biochemistry · 2025Article
- The β-adrenergic receptor-SGK1 signaling pathway in brown adipocytes protects GOT1 from proteasomal degradation.Frontiers in cell and developmental biology · 2025Article
- The effects of CypA on apoptosis: potential target for the treatment of diseases.Applied microbiology and biotechnology · 2024Review
- Review
- Bio-Pathological Functions of Posttranslational Modifications of Histological Biomarkers in Breast Cancer.Molecules (Basel, Switzerland) · 2024Review
- Article
- Harnessing function of EMT in cancer drug resistance: a metastasis regulator determines chemotherapy response.Cancer metastasis reviews · 2024Review
- δ-catenin promotes Twist1 stabilization in prostate cancer through ubiquitination modification.American journal of cancer research · 2024Article
- FBXO3 stabilizes USP4 and Twist1 to promote PI3K-mediated breast cancer metastasis.PLoS biology · 2023Article
102 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Twist1, a basic helix-loop-helix transcription factor, promotes breast tumor cell epithelial-mesenchymal transition (EMT), invasiveness, and metastasis. However, the mechanisms responsible for regulating Twist1 stability are unknown in these cells. We identified the serine 68 (Ser 68) as a major phosphorylation site of Twist1 by mass spectrometry and with specific antibodies. This Ser 68 is phosphorylated by p38, c-Jun N-terminal kinases (JNK), and extracellular signal-regulated kinases1/2 in vitro, and its phosphorylation levels positively correlate with Twist1 protein levels in human embryonic kidney 293 and breast cancer cells. Prevention of Ser 68 phosphorylation by an alanine (A) mutation (Ser 68A) dramatically accelerates Twist1 ubiquitination and degradation. Furthermore, activation of mitogen-activated protein kinases (MAPK) by an active Ras protein or TGF-β treatment significantly increases Ser 68 phosphorylation and Twist1 protein levels without altering Twist1 mRNA expression, whereas blocking of MAPK activities by either specific inhibitors or dominant negative inhibitory mutants effectively reduces the levels of both induced and uninduced Ser 68 phosphorylation and Twist protein. Accordingly, the mammary epithelial cells expressing Twist1 exhibit much higher degrees of EMT and invasiveness on stimulation with TGF-β or the active Ras and paclitaxel resistance compared with the same cells expressing the Ser 68A-Twist1 mutant. Importantly, the levels of Ser 68 phosphorylation in the invasive human breast ductal carcinomas positively correlate with the levels of Twist1 protein and JNK activity and are significantly higher in progesterone receptor-negative and HER2-positive breast cancers. These findings suggest that activation of MAPKs by tyrosine kinase receptors and Ras signaling pathways may substantially promote breast tumor cell EMT and metastasis via phoshorylation and stabilization of Twist1.
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Registered trials
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