{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T17:24:54Z","timestamp":1790011494092,"version":"4.0.1"},"reference-count":32,"publisher":"Portland Press Ltd.","issue":"1","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2012,2,1]]},"abstract":"<jats:p>The transcription factor Twist plays vital roles during embryonic development through regulating\/controlling cell migration. However, postnatally, in normal physiological settings, Twist is either not expressed or inactivated. Increasing evidence shows a strong correlation between Twist reactivation and both cancer progression and malignancy, where the transcriptional activities of Twist support cancer cells to disseminate from primary tumours and subsequently establish a secondary tumour growth in distant organs. However, it is largely unclear how this signalling programme is reactivated or what signalling pathways regulate its activity. The present review discusses recent advances in Twist regulation and activity, with a focus on phosphorylation-dependent Twist activity, potential upstream kinases and the contribution of these factors in transducing biological signals from upstream signalling complexes. The recent advances in these areas have shed new light on how phosphorylation-dependent regulation of the Twist proteins promotes or suppresses Twist activity, leading to differential regulation of Twist transcriptional targets and thereby influencing cell fate.<\/jats:p>","DOI":"10.1042\/bst20110678","type":"journal-article","created":{"date-parts":[[2012,1,19]],"date-time":"2012-01-19T15:27:25Z","timestamp":1326986845000},"page":"90-93","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Phosphorylation of basic helix\u2013loop\u2013helix transcription factor Twist in development and disease"],"prefix":"10.1042","volume":"40","author":[{"given":"Gongda","family":"Xue","sequence":"first","affiliation":[{"name":"Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian\u00a0A.","family":"Hemmings","sequence":"additional","affiliation":[{"name":"Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2012,1,19]]},"reference":[{"key":"2021111720293209800_B1","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.cell.2009.11.007","article-title":"Epithelial\u2013mesenchymal transitions in development and disease","volume":"139","author":"Thiery","year":"2009","journal-title":"Cell"},{"key":"2021111720293209800_B2","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1016\/j.devcel.2008.05.009","article-title":"Epithelial\u2013mesenchymal transition: at the crossroads of development and tumor metastasis","volume":"14","author":"Yang","year":"2008","journal-title":"Dev. Cell"},{"key":"2021111720293209800_B3","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1038\/nrm1175","article-title":"Diverse cellular and molecular mechanisms contribute to epithelial plasticity and metastasis","volume":"4","author":"Grunert","year":"2003","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2021111720293209800_B4","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1172\/JCI36183","article-title":"Biomarkers for epithelial\u2013mesenchymal transitions","volume":"119","author":"Zeisberg","year":"2009","journal-title":"J. Clin. Invest."},{"key":"2021111720293209800_B5","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/S0378-1119(01)00893-9","article-title":"A Twist in fate: evolutionary comparison of Twist structure and function","volume":"287","author":"Castanon","year":"2002","journal-title":"Gene"},{"key":"2021111720293209800_B6","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1101\/gad.9.6.686","article-title":"twist is required in head mesenchyme for cranial neural tube morphogenesis","volume":"9","author":"Chen","year":"1995","journal-title":"Genes Dev."},{"key":"2021111720293209800_B7","doi-asserted-by":"crossref","first-page":"76","DOI":"10.4161\/cc.2.2.338","article-title":"A new twist on twist: modulation of the NF-\u03baB pathway","volume":"2","author":"Sosic","year":"2003","journal-title":"Cell Cycle"},{"key":"2021111720293209800_B8","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/S0092-8674(03)00002-3","article-title":"Twist regulates cytokine gene expression through a negative feedback loop that represses NF-\u03baB activity","volume":"112","author":"Sosic","year":"2003","journal-title":"Cell"},{"key":"2021111720293209800_B9","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/j.cell.2004.06.006","article-title":"Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis","volume":"117","author":"Yang","year":"2004","journal-title":"Cell"},{"key":"2021111720293209800_B10","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1086\/301855","article-title":"Genetic heterogeneity of Saethre\u2013Chotzen syndrome, due to TWIST and FGFR mutations","volume":"62","author":"Paznekas","year":"1998","journal-title":"Am. J. Hum. Genet."},{"key":"2021111720293209800_B11","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/ng1525","article-title":"Altered Twist1 and Hand2 dimerization is associated with Saethre\u2013Chotzen syndrome and limb abnormalities","volume":"37","author":"Firulli","year":"2005","journal-title":"Nat. Genet."},{"key":"2021111720293209800_B12","doi-asserted-by":"crossref","first-page":"3347","DOI":"10.1101\/gad.1492806","article-title":"Regulation of cardiac growth and coronary angiogenesis by the Akt\/PKB signaling pathway","volume":"20","author":"Shiojima","year":"2006","journal-title":"Genes Dev."},{"key":"2021111720293209800_B13","doi-asserted-by":"crossref","first-page":"2032","DOI":"10.1161\/CIRCULATIONAHA.106.615138","article-title":"Akt signaling and growth of the heart","volume":"113","author":"Walsh","year":"2006","journal-title":"Circulation"},{"key":"2021111720293209800_B14","doi-asserted-by":"crossref","first-page":"2108","DOI":"10.1172\/JCI24682","article-title":"Disruption of coordinated cardiac hypertrophy and angiogenesis contributes to the transition to heart failure","volume":"115","author":"Shiojima","year":"2005","journal-title":"J. Clin. Invest."},{"key":"2021111720293209800_B15","doi-asserted-by":"crossref","first-page":"20814","DOI":"10.1074\/jbc.M500528200","article-title":"The FOXO3a transcription factor regulates cardiac myocyte size downstream of AKT signaling","volume":"280","author":"Skurk","year":"2005","journal-title":"J. Biol. Chem."},{"key":"2021111720293209800_B16","first-page":"31","article-title":"Protein kinase B (PKB\/Akt), a key mediator of the PI3K signaling pathway","volume":"346","author":"Fayard","year":"2010","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"2021111720293209800_B17","doi-asserted-by":"crossref","first-page":"e19251","DOI":"10.1371\/journal.pone.0019251","article-title":"Phosphorylation of the Twist1-family basic helix\u2013loop\u2013helix transcription factors is involved in pathological cardiac remodeling","volume":"6","author":"Lu","year":"2011","journal-title":"PLoS ONE"},{"key":"2021111720293209800_B18","doi-asserted-by":"crossref","first-page":"2203","DOI":"10.1128\/MCB.21.6.2203-2212.2001","article-title":"Activation of Akt (protein kinase B) in mammary epithelium provides a critical cell survival signal required for tumor progression","volume":"21","author":"Hutchinson","year":"2001","journal-title":"Mol. Cell. Biol."},{"key":"2021111720293209800_B19","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.ceb.2005.02.010","article-title":"Recent advances in the protein kinase B signaling pathway","volume":"17","author":"Woodgett","year":"2005","journal-title":"Curr. Opin. Cell Biol."},{"key":"2021111720293209800_B20","doi-asserted-by":"crossref","first-page":"3554","DOI":"10.1038\/onc.2010.115","article-title":"PKB\/AKT phosphorylation of the transcription factor Twist-1 at Ser42 inhibits p53 activity in response to DNA damage","volume":"29","author":"Vichalkovski","year":"2010","journal-title":"Oncogene"},{"key":"2021111720293209800_B21","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.ccr.2008.06.005","article-title":"Induction of EMT by twist proteins as a collateral effect of tumor-promoting inactivation of premature senescence","volume":"14","author":"Ansieau","year":"2008","journal-title":"Cancer Cell"},{"key":"2021111720293209800_B22","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.ccr.2008.06.012","article-title":"Deregulating EMT and senescence: double impact by a single twist","volume":"14","author":"Smit","year":"2008","journal-title":"Cancer Cell"},{"key":"2021111720293209800_B23","doi-asserted-by":"crossref","first-page":"2090","DOI":"10.4161\/cc.7.14.6324","article-title":"TWIST activation by hypoxia inducible factor-1 (HIF-1): implications in metastasis and development","volume":"7","author":"Yang","year":"2008","journal-title":"Cell Cycle"},{"key":"2021111720293209800_B24","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1038\/ncb1691","article-title":"Direct regulation of TWIST by HIF-1\u03b1 promotes metastasis","volume":"10","author":"Yang","year":"2008","journal-title":"Nat. Cell Biol."},{"key":"2021111720293209800_B25","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1146\/annurev.pathol.1.110304.100224","article-title":"Tumor stroma and regulation of cancer development","volume":"1","author":"Tlsty","year":"2006","journal-title":"Annu. Rev. Pathol."},{"key":"2021111720293209800_B26","doi-asserted-by":"crossref","first-page":"5792","DOI":"10.1158\/1078-0432.CCR-03-0317","article-title":"Casein kinase II \u03b1 subunit and C1-inhibitor are independent predictors of outcome in patients with squamous cell carcinoma of the lung","volume":"10","author":"O-charoenrat","year":"2004","journal-title":"Clin. Cancer Res."},{"key":"2021111720293209800_B27","doi-asserted-by":"crossref","first-page":"1698","DOI":"10.1182\/blood-2005-11-013672","article-title":"Multiple myeloma cell survival relies on high activity of protein kinase CK2","volume":"108","author":"Piazza","year":"2006","journal-title":"Blood"},{"key":"2021111720293209800_B28","doi-asserted-by":"crossref","first-page":"e19412","DOI":"10.1371\/journal.pone.0019412","article-title":"IL-6 stabilizes Twist and enhances tumor cell motility in head and neck cancer cells through activation of casein kinase 2","volume":"6","author":"Su","year":"2011","journal-title":"PLoS ONE"},{"key":"2021111720293209800_B29","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/s10555-010-9208-5","article-title":"The role of MAP kinases and MAP kinase phosphatase-1 in resistance to breast cancer treatment","volume":"29","author":"Haagenson","year":"2010","journal-title":"Cancer Metastasis Rev."},{"key":"2021111720293209800_B30","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1038\/nrc2694","article-title":"Signal integration by JNK and p38 MAPK pathways in cancer development","volume":"9","author":"Wagner","year":"2009","journal-title":"Nat. Rev. Cancer"},{"key":"2021111720293209800_B31","doi-asserted-by":"crossref","first-page":"3920","DOI":"10.1128\/MCB.01219-06","article-title":"Upregulation of Twist-1 by NF-\u03baB blocks cytotoxicity induced by chemotherapeutic drugs","volume":"27","author":"Pham","year":"2007","journal-title":"Mol. Cell. Biol."},{"key":"2021111720293209800_B32","doi-asserted-by":"crossref","first-page":"3980","DOI":"10.1158\/0008-5472.CAN-10-2914","article-title":"Phosphorylation of serine 68 of Twist1 by MAPKs stabilizes Twist1 protein and promotes breast cancer cell invasiveness","volume":"71","author":"Hong","year":"2011","journal-title":"Cancer Res."}],"container-title":["Biochemical Society Transactions"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/biochemsoctrans\/article-pdf\/40\/1\/90\/486638\/bst0400090.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemsoctrans\/article-pdf\/40\/1\/90\/486638\/bst0400090.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,18]],"date-time":"2021-11-18T00:31:52Z","timestamp":1637195512000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemsoctrans\/article\/40\/1\/90\/66307\/Phosphorylation-of-basic-helix-loop-helix"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,1,19]]},"references-count":32,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2012,1,19]]},"published-print":{"date-parts":[[2012,2,1]]}},"URL":"https:\/\/doi.org\/10.1042\/bst20110678","relation":{},"ISSN":["0300-5127","1470-8752"],"issn-type":[{"value":"0300-5127","type":"print"},{"value":"1470-8752","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,1,19]]}}}