ITGA3 与 VASP 相互作用，调节乳腺癌细胞的干性和上皮-间充质转化。
ITGA3 interacts with VASP to regulate stemness and epithelial-mesenchymal transition of breast cancer cells.
机构信息
Department of Pathology, Dalian Medical University, Dalian 116044, China.
Department of General Surgery, The First Affiliated Hospital, Dalian Medical University, Dalian 116011, China.
出版信息
Gene. 2020 Apr 15;734:144396. doi: 10.1016/j.gene.2020.144396. Epub 2020 Jan 25.
BACKGROUND
The interaction of integrin and extracellular matrix (ECM) has a profound implication on pathological conditions such as tumor growth and infiltration. Related reports have confirmed that integrin α3 (ITGA3) influences the development of bladder cancer, head and neck cancer, colorectal cancer and other cancers. However, the mechanism of ITGA3 in breast cancer is unknown.
METHODS
The impact of ITGA3 on the biological features of breast cancer cells was explored using the Transwell and wound healing assays. In addition, its influence on stemness of breast cancer cells was examined with the sphere formation assay. The possible mechanism by which ITGA3 regulates breast cancer was explored using Western blot. The interaction between ITGA3 and VASP was determined by co-immunoprecipitation and immunofluorescence staining assays.
RESULTS
Results show that downregulation of ITGA3 promotes breast cancer cell proliferation, apoptosis, invasion and migration. Indeed, suppression of ITGA3 negatively regulates the stemness of breast cancer cells and EMT process. Our findings indicate that ITGA3 interacts with VASP and regulates its expression, and knockdown of ITGA3 inhibits the activity of the PI3K-AKT axis.
CONCLUSION
Our results show that ITGA3-VASP modulates breast cancer cell stemness, EMT and PI3K-AKT pathways. Therefore, ITGA3 might be a druggable target for clinical breast cancer management.
背景
整合素与细胞外基质（ECM）的相互作用对肿瘤生长和浸润等病理状况有深远影响。相关报道已经证实整合素 α3（ITGA3）影响膀胱癌、头颈部癌、结直肠癌等多种癌症的发展。然而，ITGA3 在乳腺癌中的作用机制尚不清楚。
方法
使用 Transwell 和划痕愈合实验探讨 ITGA3 对乳腺癌细胞生物学特性的影响。此外，还通过球体形成实验研究了其对乳腺癌细胞干性的影响。使用 Western blot 探讨 ITGA3 调节乳腺癌的可能机制。通过免疫共沉淀和免疫荧光染色实验确定 ITGA3 与 VASP 的相互作用。
结果
结果表明，下调 ITGA3 可促进乳腺癌细胞的增殖、凋亡、侵袭和迁移。事实上，抑制 ITGA3 可负调控乳腺癌细胞的干性和 EMT 过程。我们的研究结果表明，ITGA3 与 VASP 相互作用并调节其表达，敲低 ITGA3 可抑制 PI3K-AKT 轴的活性。
结论
我们的研究结果表明，ITGA3-VASP 调节乳腺癌细胞的干性、EMT 和 PI3K-AKT 通路。因此，ITGA3 可能是临床乳腺癌管理的一个有治疗潜力的靶点。
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