Apoptosis-linked gene 2 promotes breast cancer growth and metastasis by regulating the cytoskeleton

// Juan Qin 1 , Dengwen Li 1 , Yunqiang Zhou 1 , Songbo Xie 2 , Xin Du 2 , Ziwei Hao 1 , Ruming Liu 1 , Xinqi Liu 1 , Min Liu 2 , Jun Zhou 1, 2 1 State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials of the Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071, China 2 Institute of Biomedical Sciences, College of Life Sciences, Key Laboratory of Animal Resistance Biology of Shandong Province, Shandong Normal University, Jinan 250014, China Correspondence to: Jun Zhou, email: junzhou@nankai.edu.cn Keywords: breast cancer, growth, metastasis, cell proliferation, cell migration Received: October 26, 2016      Accepted: November 24, 2016      Published: December 01, 2016 ABSTRACT Breast cancer is the most prevalent cancer in women. Although it begins as local disease, breast cancer frequently metastasizes to the lymph nodes and distant organs. Therefore, novel therapeutic targets are needed for the management of this disease. Apoptosis-linked gene 2 (ALG-2) is a calcium-binding protein crucial for diverse physiological processes and has recently been implicated in cancer development. However, it remains unclear whether this protein is involved in the pathogenesis of breast cancer. Here, we demonstrate that the expression of ALG-2 is significantly upregulated in breast cancer tissues and is correlated with clinicopathological characteristics indicative of tumor malignancy. Our data further show that ALG-2 stimulates breast cancer growth and metastasis in mice. ALG-2 also promotes breast cancer cell proliferation, survival, and motility in vitro . Mechanistic data reveal that ALG-2 disrupts the localization of centrosome proteins, resulting in spindle multipolarity and chromosome missegregation. In addition, ALG-2 drives the polarization and migration of breast cancer cells by facilitating the rearrangement of microtubules and microfilaments. These findings reveal a critical role for ALG-2 in the pathogenesis of breast cancer and have important implications for its diagnosis and therapy.