ArticleJournal of the National Cancer Institute2010
KLF6 Gene and early melanoma development in a collagen I-rich extracellular environment.
Article in Journal of the National Cancer Institute, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 16 citations in OpenAlex.
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- Deciphering Collagen Phenotype Dynamics Regulators: Insights from In-Silico Analysis.Journal of bioinformatics and systems biology : Open access · 2024Article
- A genome-wide genetic screen uncovers determinants of human pigmentation.Science (New York, N.Y.) · 2023Article
- Decreased expression of miR-204-3p in peripheral blood and wound margin tissue associated with the onset and poor wound healing of diabetic foot ulcers.International wound journal · 2023Article
- Loss of ADAM9 Leads to Modifications of the Extracellular Matrix Modulating Tumor Growth.Biomolecules · 2020Article
- Identification of glycogen synthase kinase 3α as a therapeutic target in melanoma.Pigment cell & melanoma research · 2013Article
- Krüppel-like factors in cancer.Nature reviews. Cancer · 2013Review
- Current and future trials of targeted therapies in cutaneous melanoma.Advances in experimental medicine and biology · 2013Review
- Transcription factors Sp1 and p73 control the expression of the proapoptotic protein NOXA in the response of testicular embryonal carcinoma cells to cisplatin.The Journal of biological chemistry · 2012Article
- Uncover disease genes by maximizing information flow in the phenome-interactome network.Bioinformatics (Oxford, England) · 2011Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundA putative tumor suppressor gene at chromosome 10p15, which contains KLF6 and other genes, is predicted to be lost during melanoma development, and its identity is unknown. In this study, we investigated the biological roles and identity of this tumor suppressor gene.
methodsThe human UACC 903 melanoma cell line containing introduced DNA fragments from the 10p15 region with (10E6/3, 10E6/11, and 10E6/18) and without (10ER4S.2/1) the tumor suppressor gene was used. Xenograft tumors were generated in a total of 40 mice with melanoma cell lines, and tumor size was measured. Cells were cultured on plastic or a gel of type I collagen. Viability, proliferation, and apoptosis were assessed. Expression of KLF6 protein was assessed by immunohistochemistry and immunoblot analysis. Expression of phosphorylated Erk1/2 and cyclin D1 was assessed by immunoblot analysis. Protein expression of KLF6 was inhibited with small interfering RNA (siRNA). KLF6 protein expression was assessed in 17 human nevi and human melanoma specimens from 29 patients. Statistical analyses were adjusted for multiple comparisons by use of Dunnett method. All statistical tests were two-sided.
resultsMelanoma cells containing KLF6 generated smaller subcutaneous xenograft tumors with fewer proliferating cells than control cells. When grown on collagen 1, viability of cells with ectopic KLF6 expression (72%) was lower than that of control cells (100%) (group difference = -28%, 95% confidence interval = -31.3% to -25.2%, P < .001). Viability of melanoma cells with or without the KLF6 tumor suppressor gene on plastic dishes was similar. When KLF6 expression was inhibited with KLF6 siRNA, viability of cells with the tumor suppressor gene on collagen I gel increased compared with that of control cells carrying scrambled siRNA. KLF6 protein was detected in all nevi examined but not in human metastatic melanoma tissue examined. Ectopic expression of KLF6 protein in melanoma cells grown on collagen I decreased levels of phosphorylated Erk1/2 and cyclin D1 in the mitogen-activated protein kinase signaling pathway.
conclusionsIn melanoma cells, the tumor suppressor gene at 10p15 appears to be KLF6. Signaling from the collagen I-rich extracellular matrix appears to be involved in the tumor suppressive activity of KLF6 protein.
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