ArticleTranslational oncology2009
Tissue inhibitor of metalloproteinase 1 expression associated with gene demethylation confers anoikis resistance in early phases of melanocyte malignant transformation.
Article in Translational oncology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 33 citations in OpenAlex.
- LncRNAEpigenetics · 2026Article
- The Dual Roles of TIMP-1 in Cancer: From Protease Inhibition to Cytokine Signaling.Molecular biology reports · 2026Review
- Epigenetic alterations in cancer metastasis: molecular mechanisms and implications for precision oncology.Frontiers in oncology · 2026Review
- Predictive value of immunomodulatory-related genes for the prognosis of lung adenocarcinoma based on bioinformatics analysis.Discover oncology · 2025Article
- TIMP1 Overexpression in Ovarian Cancer Spheroids: Implications for Prognosis, Resistance, and Metastatic Potential.Cancers · 2025Article
- LncRNAs in melanoma phenotypic plasticity: emerging targets for promising therapies.RNA biology · 2024Review
- Therapeutic targeting of anoikis resistance in cutaneous melanoma metastasis.Frontiers in cell and developmental biology · 2023Review
- Genes regulated by DNA methylation are involved in distinct phenotypes during melanoma progression and are prognostic factors for patients.Molecular oncology · 2022Article
- Regulation of Tumor Metabolism and Extracellular Acidosis by the TIMP-10-CD63 Axis in Breast Carcinoma.Cells · 2021Article
- Review
- Characteristics of TIMP1, CD63, and β1-Integrin and the Functional Impact of Their Interaction in Cancer.International journal of molecular sciences · 2021Review
- Expression ofGenes · 2021Article
- Transcriptional signatures underlying dynamic phenotypic switching and novel disease biomarkers in a linear cellular model of melanoma progression.Neoplasia (New York, N.Y.) · 2021Article
- Inhibition of skin carcinogenesis by suppression of NF-κB dependent ITGAV and TIMP-1 expression in IL-32γ overexpressed condition.Journal of experimental & clinical cancer research : CR · 2018Article
- Article
- Variations in the expression of TIMP1, TIMP2 and TIMP3 in cutaneous melanoma with regression and their possible function as prognostic predictors.Oncology letters · 2016Article
- Higher levels of TIMP-1 expression are associated with a poor prognosis in triple-negative breast cancer.Molecular cancer · 2016Article
- Regulation of TIMP-1 in Human Placenta and Fetal Membranes by lipopolysaccharide and demethylating agent 5-aza-2'-deoxycytidine.Reproductive biology and endocrinology : RB&E · 2015Article
- Timp1 interacts with beta-1 integrin and CD63 along melanoma genesis and confers anoikis resistance by activating PI3-K signaling pathway independently of Akt phosphorylation.Molecular cancer · 2013Article
- Down-regulation of ANAPC13 and CLTCL1: Early Events in the Progression of Preinvasive Ductal Carcinoma of the Breast.Translational oncology · 2012Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although anoikis resistance has been considered a hallmark of malignant phenotype, the causal relation between neoplastic transformation and anchorage-independent growth remains undefined. We developed an experimental model of murine melanocyte malignant transformation, where a melanocyte lineage (melan-a) was submitted to sequential cycles of anchorage blockade, resulting in progressive morphologic alterations, and malignant transformation. Throughout this process, cells corresponding to premalignant melanocytes and melanoma cell lines were established and show progressive anoikis resistance and increased expression of Timp1. In melan-a melanocytes, Timp1 expression is suppressed by DNA methylation as indicated by its reexpression after 5-aza-2'-deoxycytidine treatment. Methylation-sensitive single-nucleotide primer extension analysis showed increased demethylation in Timp1 in parallel with its expression along malignant transformation. Interestingly, TIMP1 expression has already been related with negative prognosis in some human cancers. Although described as a MMP inhibitor, this protein has been associated with apoptosis resistance in different cell types. Melan-a cells overexpressing Timp1 showed increased survival in suspension but were unable to form tumors in vivo, whereas Timp1-overexpressing melanoma cells showed reduced latency time for tumor appearance and increased metastatic potential. Here, we demonstrated for the first time an increment in Timp1 expression since the early phases of melanocyte malignant transformation, associated to a progressive gene demethylation, which confers anoikis resistance. In this way, Timp1 might be considered as a valued marker for melanocyte malignant transformation.
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Registered trials
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