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ITGA2 promotes expression of ACLY and CCND1 in enhancing breast cancer stemness and metastasis

Genes & Diseases 2021年第4期8卷 493-508页

作者： Valery Adorno-Cruz Andrew D.Hoffmann Xia Liu Nurmaa K.Dashzeveg Rokana Taftaf Brian Wray ruth a.keri Huiping Liu Department of Pharmacology Case Western Reserve UniversityClevelandOH 11318USA Department of Pharmacology Northwestern University Feinberg School of MedicineChicagoIL 60611USA University of Kentucky College of MedicineLexingtonKY 40536USA Bioinformatic Core Northwestern University Feinberg School of MedicineChicagoIL 60611USA Department of Genetics and Genome Sciences The Division of General Medical Sciences-OncologyCase Western Reserve UniversityClevelandOH 11318USA Department of Medicine The Division of Hematology and OncologyNorthwestern University Feinberg School of MedicineChicagoIL 60611USA Lurie Comprehensive Cancer Center Northwestern University Feinberg School of MedicineChicagoIL 60611USA Department of Pathology and Case Comprehensive Cancer Center Case Western Reserve UniversityClevelandOH 11318USA

Cancer metastasis is largely incurable and accounts for 90%of breast cancer deaths,especially for the aggressive basal-like or triple negative breast cancer(TNBC).Combining patient database analyses and functional studies,we examined the association of integrin family members with clinical outcomes as well as their connection with previously identified microRNA regulators of metastasis,such as miR-206 that inhibits stemness and metastasis of *** we report that the integrin receptor CD49b-encoding ITGA2,a direct target of miR-206,promotes breast cancer stemness and ***2 knockdown sup-pressed self-renewal related mammosphere formation and pluripotency marker expression,in-hibited cell cycling,compromised migration and invasion,and therefore decreased lung metastasis of breast ***2 overexpression reversed miR-206-caused cell cycle arrest in *** sequencing analyses revealed that ITGA2 knockdown inhibits genes related to cell cycle regulation and lipid metabolism,including CCND1 and ACLY as representative targets,*** of CCND1 or ACLY inhibits mammosphere formation of breast cancer *** of CCND1 rescues the phenotype of ITGA2 knockdown-induced cell cycle ***-encoded ATP citrate lyase is essential to maintain cellular acetyl-CoA ***1 knockdown further mimics 1TGA2 knodkdown in abolishing lung colonization of breast cancer *** identified that the low levels of miR-206 as well as high expression levels of 1TGA2,ACLY and CCND1 are associated with an unf avor able relapse-free survival of the pa-tients with estrogen receptor-negative or high grade breast cancer,especially basal-like or TNBC,possibly serving as potential biomarkers of cancer stemness and thera peutic targets of breast cancer metastasis.

关键词： ACLY Breast cancer CCND1 CD49b Integrins ITGA2 Metastasis Stemness

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A new view of the mammary epithelial hierarchy and its implications for breast cancer initiation and metastasis

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Journal of Cancer Metastasis and Treatment 2019年第6期4卷 55-70页

作者： Lindsey J.Anstine ruth keri Department of Pharmacology Case Western Reserve UniversityClevelandOH 44106USA Department of Genetics and Genome Sciences and Department of General Medical Sciences-Oncology Case Western Reserve UniversityClevelandOH 44106USA

The existence of mammary epithelial stem cell(MaSC)populations capable of mediating mammary gland development and homeostasis has been established for over a decade.A combination of lineage tracing and mammary gland transplantation studies has affirmed that MaSCs and their downstream progenitors are organized in a hierarchal manner;however,these techniques have failed to illuminate the complete spectrum of epithelial intermediate populations or their spatial and temporal *** advent of single cell sequencing technology has allowed for characterization of highly heterogeneous tissues at high *** the last two years,the remarkable advances in single cell RNA sequencing technologies have been leveraged to address the heterogeneity of the mammary *** studies have afforded fresh insights into the transcriptional differentiation hierarchy and its ***,these data have led to a major conceptual shift in which the rigid boundaries separating stem,progenitor,and differentiated epithelial populations have been deconstructed,resulting in a new more fluid and flexible model of epithelial *** emerging view of the mammary epithelial hierarchy has important implications for mammary development,carcinogenesis,and metastasis,providing novel insights into the underlying cellular states that may promote malignant phenotypes.

关键词： Mammary gland mammary epithelial cells breast cancer stem cell

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Therapeutic silencing of miR-lOb inhibits metastasis in a mouse mammary tumor model

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中国肿瘤临床 2010年第15期37卷 905-905页

作者： ruth keri Case Westem Reserve University

Ma L, Reinhardt F, Pan E, Soutschek J, Bhat B,Marcusson EG, Teruya-Feldstein J, Bell GW,Weinberg RA Nat Biotechnol 2010 Apr 28(4):341-7 Faculty Comments & Author Responses Facullty Member

关键词： Therapeutic silencing of miR-lOb inhibits metastasis in a mouse mammary tumor model

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