Gab2 Ablation Reverses the Stemness of HER2-Overexpressing Breast Cancer Cells

• Main Authors: Peng Zhang, Yiying Chen, Miaomiao Gong, Zhumei Zhuang, Yueyue Wang, Lin Mu, Tianjiao Wang, Jinjin Pan, Yanan Liu, Jianming Xu, Rui Liang, Yuhui Yuan
• Format: Article
• Language: English
• Published: Cell Physiol Biochem Press GmbH & Co KG 2018-10-01
• Series: Cellular Physiology and Biochemistry
• Subjects: Gab2; HER2; Cancer stem cells; Breast cancer
• Online Access: https://www.karger.com/Article/FullText/493957

Background/Aims: HER2 has been implicated in mammary tumorigenesis as well as aggressive tumor growth and metastasis. Its overexpression is related to a poor prognosis and chemoresistance in breast cancer patients. Although Grb2-associated binding protein 2 (Gab2) is important in the development and progression of human cancer, its effects and mechanisms in HER2-overexpressing breast cancer are unclear. Methods: Clone formation and MTT assays were used to examine cell proliferation. To detect the effect of Gab2 on the stemness of breast cancer cells, we used flow cytometry, a sphere formation assay, real-time PCR, and western blot. An animal model was created to validate the effect of Gab2 on tumor growth in vivo. Tissue slides were analyzed by immunohistochemistry. Results: Knockdown of Gab2 suppressed PI3K/AKT and MAPK/ERK pathway activity. Gab2 ablation also reduced the stemness of HER2-overexpressing breast cancer cells. In vivo, knockdown of Gab2 inhibited tumor growth. Conclusion: This study unveils a potential function of Gab2 in HER2-overexpressing breast cancer cells. Gab2 might be a potential target in the clinical therapy of HER2-overexpressing breast carcinoma.