دورية أكاديمية
أعرض في EDS

NDRG4 promoter hypermethylation is a mechanistic biomarker associated with metastatic progression in breast cancer patients.

التفاصيل البيبلوغرافية
العنوان: NDRG4 promoter hypermethylation is a mechanistic biomarker associated with metastatic progression in breast cancer patients.
المؤلفون: Jandrey EHF; 1Centro de Oncologia Molecular, Hospital Sírio-Libanês, São Paulo, SP Brazil., Moura RP; 2Ludwig Institute for Cancer Research (LICR), São Paulo, Brazil., Andrade LNS; 3Laboratório de Oncologia Experimental, Centro de Investigação Translacional em Oncologia, Instituto do Câncer do Estado de São Paulo, São Paulo, SP Brazil., Machado CL; 3Laboratório de Oncologia Experimental, Centro de Investigação Translacional em Oncologia, Instituto do Câncer do Estado de São Paulo, São Paulo, SP Brazil., Campesato LF; 1Centro de Oncologia Molecular, Hospital Sírio-Libanês, São Paulo, SP Brazil., Leite KRM; 4Laboratório de Patologia, Hospital Sírio-Libanês, São Paulo, SP Brazil., Inoue LT; 1Centro de Oncologia Molecular, Hospital Sírio-Libanês, São Paulo, SP Brazil., Asprino PF; 1Centro de Oncologia Molecular, Hospital Sírio-Libanês, São Paulo, SP Brazil., da Silva APM; 2Ludwig Institute for Cancer Research (LICR), São Paulo, Brazil., de Barros ACSD; 5Departamento de Mastologia, Hospital Sírio-Libanês, São Paulo, Brazil., Carvalho A; 6Hospital do Câncer de Barretos, Barretos, SP Brazil., de Lima VC; 7Centro Internacional de Pesquisa, A.C. Camargo Cancer Center, Fundação Antônio Prudente, São Paulo, SP Brazil., Carraro DM; 7Centro Internacional de Pesquisa, A.C. Camargo Cancer Center, Fundação Antônio Prudente, São Paulo, SP Brazil., Brentani HP; 8LIM23-Instituto de Psiquiatria, Faculdade de Medicina da Universidade de São Paulo (USP), São Paulo, Brazil., da Cunha IW; Rede D'OR, Hospital São Luis, São Paulo, SP Brazil., Soares FA; Rede D'OR, Hospital São Luis, São Paulo, SP Brazil., Parmigiani RB; 2Ludwig Institute for Cancer Research (LICR), São Paulo, Brazil., Chammas R; 3Laboratório de Oncologia Experimental, Centro de Investigação Translacional em Oncologia, Instituto do Câncer do Estado de São Paulo, São Paulo, SP Brazil., Camargo AA; 1Centro de Oncologia Molecular, Hospital Sírio-Libanês, São Paulo, SP Brazil.; 2Ludwig Institute for Cancer Research (LICR), São Paulo, Brazil., Costa ÉT; 1Centro de Oncologia Molecular, Hospital Sírio-Libanês, São Paulo, SP Brazil.; 2Ludwig Institute for Cancer Research (LICR), São Paulo, Brazil.
المصدر: NPJ breast cancer [NPJ Breast Cancer] 2019 Apr 05; Vol. 5, pp. 11. Date of Electronic Publication: 2019 Apr 05 (Print Publication: 2019).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Breast Cancer Research Foundation Country of Publication: United States NLM ID: 101674891 Publication Model: eCollection Cited Medium: Print ISSN: 2374-4677 (Print) Linking ISSN: 23744677 NLM ISO Abbreviation: NPJ Breast Cancer Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: New York, NY : Breast Cancer Research Foundation : Nature Publishing Group, [2015]-
مستخلص: The risk of developing metastatic disease in breast cancer patients is traditionally predictable based on the number of positive axillary lymph nodes, complemented with additional clinicopathological factors. However, since lymph node-negative patients have a 20-30% probability of developing metastatic disease, lymph node information alone is insufficient to accurately assess individual risk. Molecular approaches, such as multigene expression panels, analyze a set of cancer-related genes that more accurately predict the early risk of metastasis and the treatment response. Here, we present N-Myc downstream-regulated gene 4 (NDRG4) epigenetic silencing as a mechanistic biomarker of metastasis in ductal invasive breast tumors. While aberrant NDRG4 DNA hypermethylation is significantly associated with the development of metastatic disease, downregulation of NDRG4 transcription and protein expression is functionally associated with enhanced lymph node adhesion and cell mobility. Here, we show that epigenetic silencing of NDRG4 modulates integrin signaling by assembling β1-integrins into large punctate clusters at the leading edge of tumor cells to promote an "adhesive switch," decreasing cell adhesion to fibronectin and increasing cell adhesion and migration towards vitronectin, an important component of human lymph nodes. Taken together, our functional and clinical observations suggest that NDRG4 is a potential mechanistic biomarker in breast cancer that is functionally associated with metastatic disease.
Competing Interests: The authors declare no competing interests.
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تواريخ الأحداث: Date Created: 20190410 Latest Revision: 20231006
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC6450950
DOI: 10.1038/s41523-019-0106-x
PMID: 30963110
قاعدة البيانات: MEDLINE
الوصف
تدمد:2374-4677
DOI:10.1038/s41523-019-0106-x