Apoptosis-linked gene 2 promotes breast cancer growth and metastasis by regulating the cytoskeleton.
Apoptosis-linked gene 2 promotes breast cancer growth and metastasis by regulating the cytoskeleton.
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凋亡相关基因2通过调节细胞骨架促进乳腺癌生长和转移
DOI：
10.18632/oncotarget.13740
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发表时间：
2017-01-10
期刊：
影响因子：
--
通讯作者：
Zhou J
中科院分区：
文献类型：
--
作者：
Qin J;Li D;Zhou Y;Xie S;Du X;Hao Z;Liu R;Liu X;Liu M;Zhou J
乳腺癌是女性中最常见的癌症。虽然一开始是局部疾病，但乳腺癌经常转移到淋巴结和远处器官。因此，需要新的治疗靶点来治疗这种疾病。凋亡相关基因2 （ALG-2）是一种钙结合蛋白，对多种生理过程至关重要，最近被认为与癌症的发展有关。然而，目前尚不清楚这种蛋白是否与乳腺癌的发病机制有关。在这里，我们证明了ag -2在乳腺癌组织中的表达显著上调，并与肿瘤恶性的临床病理特征相关。我们的数据进一步表明，ALG-2刺激小鼠乳腺癌的生长和转移。ag -2还能促进乳腺癌细胞的增殖、存活和体外运动。机制数据显示，ALG-2破坏中心体蛋白的定位，导致纺锤体多极性和染色体错分离。此外，ag -2通过促进微管和微丝的重排来驱动乳腺癌细胞的极化和迁移。这些发现揭示了ag -2在乳腺癌发病机制中的关键作用，并对其诊断和治疗具有重要意义。
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.