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Integrin α5 down-regulation by miR-205 suppresses triple negative breast cancer stemness and metastasis by inhibiting the Src/Vav2/Rac1 pathway.

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机构: [a]Department of Toxicology and Cancer Biology, Center for Research on Environment Disease, College of Medicine, University of Kentucky, Lexington, KY, 40536, USA [b]Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510315, China [c]Department of Radiology, University of Michigan, Ann Arbor, MI, 48109, USA [d]Cancer Center, Southern Medical University, Guangzhou, Guangdong, 510315, China [e]Institute for Chemical Carcinogenesis, State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou, Guangdong, 511436, China
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关键词: Metastatic triple negative breast cancer (TNBC) microRNA-205 (miR-205) Integrin α5 (ITGA5) Rho GTPase Rac1 Cancer stem cell (CSC)-Like property

摘要:
Triple negative breast cancer (TNBC) usually displays more aggressive metastasis, the underlying mechanism is unclear. Previous studies showed that microRNA-205 (miR-205) has controversial roles in cancer, however, its role in TNBC metastasis and the underlying mechanism have not been well-understood. In this study we found that miR-205 expression level is extremely low in basal mesenchymal-like highly migratory and invasive TNBC cells. Stably re-expressing miR-205 in TNBC cells significantly reduced their migration, invasion capability and cancer stem cell (CSC)-like property. Nude mouse orthotopic mammary xenograft tumor model study revealed that miR-205 re-expression greatly decreases TNBC tumor growth and abolishes spontaneous lung metastasis. Mechanistic studies demonstrated that miR-205 inhibits TNBC cell metastatic traits and tumor metastasis by down-regulating integrin α5 (ITGA5). Moreover, ITGA5 knockout using the CRISPR/Cas9 technique achieved the same strong inhibitory effect on TNBC cell CSC-like property and tumor metastasis as re-expressing miR-205 did. Further mechanistic studies indicated that ITGA5 down-regulation by miR-205 re-expression impairs TNBC cell metastatic traits by inhibiting the Src/Vav2/Rac1 pathway. Together, our findings suggest that miR-205 and ITGA5 may serve as potential targets for developing effective therapies for metastatic TNBC. Copyright © 2018 Elsevier B.V. All rights reserved.

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出版当年[2017]版:
大类 | 2 区 医学
小类 | 2 区 肿瘤学
最新[2025]版:
大类 | 1 区 医学
小类 | 2 区 肿瘤学
第一作者:
第一作者机构: [a]Department of Toxicology and Cancer Biology, Center for Research on Environment Disease, College of Medicine, University of Kentucky, Lexington, KY, 40536, USA [b]Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510315, China [d]Cancer Center, Southern Medical University, Guangzhou, Guangdong, 510315, China
通讯作者:
通讯机构: [b]Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510315, China [d]Cancer Center, Southern Medical University, Guangzhou, Guangdong, 510315, China [*1]Cancer Center, Southern Medical University, Guangzhou, Guangdong 50315, China.
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