ArticleOncogene2011
Homeodomain protein DLX4 counteracts key transcriptional control mechanisms of the TGF-β cytostatic program and blocks the antiproliferative effect of TGF-β.
Article in Oncogene, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 40 citations in OpenAlex.
- Multi-omics analysis identifies DLX4 as a novel biomarker for diagnosis, prognosis, and immune infiltration: from pan-cancer to renal cancer.Discover oncology · 2025Article
- DNA methylation-mediated differential expression of DLX4 isoforms has opposing roles in leukemogenesis.Cellular & molecular biology letters · 2022Article
- Evaluating the Expression of Candidate Homeobox Genes and Their Role in Local-Site Inflammation in Mucosal Tissue Obtained from Children with Non-Syndromic Cleft Lip and Palate.Journal of personalized medicine · 2021Article
- TRIM22 inhibits the proliferation of gastric cancer cells through the Smad2 protein.Cell death discovery · 2021Article
- Review
- DLX1 acts as a crucial target of FOXM1 to promote ovarian cancer aggressiveness by enhancing TGF-β/SMAD4 signaling.Oncogene · 2017Article
- DLX4 hypermethylation is a prognostically adverse indicator in de novo acute myeloid leukemia.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- The homeobox gene DLX4 regulates erythro-megakaryocytic differentiation by stimulating IL-1β and NF-κB signaling.Journal of cell science · 2015Article
- The homeoprotein DLX4 stimulates NF-κB activation and CD44-mediated tumor-mesothelial cell interactions in ovarian cancer.The American journal of pathology · 2015Article
- DLX4 is associated with orofacial clefting and abnormal jaw development.Human molecular genetics · 2015Article
- The homeoprotein DLX4 controls inducible nitric oxide synthase-mediated angiogenesis in ovarian cancer.Molecular cancer · 2015Article
- Breast cancer anti-estrogen resistance 3 inhibits transforming growth factor β/Smad signaling and associates with favorable breast cancer disease outcomes.Breast cancer research : BCR · 2014Article
- The homeobox gene DLX4 promotes generation of human induced pluripotent stem cells.Scientific reports · 2014Article
- HOXA9 promotes homotypic and heterotypic cell interactions that facilitate ovarian cancer dissemination via its induction of P-cadherin.Molecular cancer · 2014Article
- Increased copy number of the DLX4 homeobox gene in breast axillary lymph node metastasis.Cancer genetics · 2014Article
- Homeobox Gene Deregulation: Impact on the Hallmarks of Cancer.Cancer hallmarks · 2013Article
- Pharmacological inhibition of myostatin/TGF-β receptor/pSmad3 signaling rescues muscle regenerative responses in mouse model of type 1 diabetes.Acta pharmacologica Sinica · 2013Article
- Dual functions of the homeoprotein DLX4 in modulating responsiveness of tumor cells to topoisomerase II-targeting drugs.Cancer research · 2013Article
- HOXA9 promotes ovarian cancer growth by stimulating cancer-associated fibroblasts.The Journal of clinical investigation · 2012Article
- A local paracrine and endocrine network involving TGFβ, Cox-2, ROS, and estrogen receptor β influences reactive stromal cell regulation of prostate cancer cell motility.Molecular endocrinology (Baltimore, Md.) · 2012Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The antiproliferative activity of transforming growth factor-β (TGF-β) is essential for maintaining normal tissue homeostasis and is lost in many types of tumors. Gene responses that are central to the TGF-β cytostatic program include activation of the cyclin-dependent kinase inhibitors, p15(Ink4B) and p21(WAF1/Cip1), and repression of c-myc. These gene responses are tightly regulated by a repertoire of transcription factors that include Smad proteins and Sp1. The DLX4 homeobox patterning gene encodes a transcription factor that is absent from most normal adult tissues, but is expressed in a wide variety of malignancies, including lung, breast, prostate and ovarian cancers. In this study, we demonstrate that DLX4 blocks the antiproliferative effect of TGF-β. DLX4 inhibited TGF-β-mediated induction of p15(Ink4B) and p21(WAF1/Cip1) expression. DLX4 bound and prevented Smad4 from forming complexes with Smad2 and Smad3, but not with Sp1. However, DLX4 also bound and inhibited DNA-binding activity of Sp1. In addition, DLX4 induced expression of c-myc independently of TGF-β/Smad signaling. The ability of DLX4 to counteract key transcriptional control mechanisms of the TGF-β cytostatic program could explain, in part, the resistance of tumors to the antiproliferative effect of TGF-β.
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