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凋亡相关基因2通过调节细胞骨架促进乳腺癌的生长和转移。

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

作者信息

Qin Juan, Li Dengwen, Zhou Yunqiang, Xie Songbo, Du Xin, Hao Ziwei, Liu Ruming, Liu Xinqi, Liu Min, Zhou Jun

机构信息

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.

Institute of Biomedical Sciences, College of Life Sciences, Key Laboratory of Animal Resistance Biology of Shandong Province, Shandong Normal University, Jinan 250014, China.

出版信息

Oncotarget. 2017 Jan 10;8(2):2745-2757. doi: 10.18632/oncotarget.13740.

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.

摘要

乳腺癌是女性中最常见的癌症。尽管乳腺癌最初是局部疾病,但它经常转移至淋巴结和远处器官。因此,需要新的治疗靶点来管理这种疾病。凋亡相关基因2(ALG-2)是一种对多种生理过程至关重要的钙结合蛋白,最近被认为与癌症发展有关。然而,这种蛋白是否参与乳腺癌的发病机制仍不清楚。在此,我们证明ALG-2在乳腺癌组织中的表达显著上调,并且与指示肿瘤恶性程度的临床病理特征相关。我们的数据进一步表明,ALG-2在小鼠中刺激乳腺癌生长和转移。ALG-2在体外也促进乳腺癌细胞增殖、存活和运动。机制研究数据显示,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,ALG-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ALG-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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8787/5356838/a8d7f8dc7e82/oncotarget-08-2745-g001.jpg

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