Leighton Ximena, Eidelman Ofer, Jozwik Catherine, Pollard Harvey B, Srivastava Meera
Department of Anatomy, Physiology and Genetics, Institute for Molecular Medicine, Center for Medical Proteomics, Uniformed Services University School of Medicine, 4301 Jones Bridge Road, Bethesda, MD, 20814, USA.
Methods Mol Biol. 2017;1513:23-35. doi: 10.1007/978-1-4939-6539-7_3.
Chromosomal abnormalities, including homozygous deletions and loss of heterozygosity at 10q, are commonly observed in most human tumors, including prostate, breast, and kidney cancers. The ANXA7-GTPase is a tumor suppressor, which is frequently inactivated by genomic alterations at 10q21. In the last few years, considerable amounts of data have accumulated describing inactivation of ANXA7-GTPase in a variety of human malignancies and demonstrating the tumor suppressor potential of ANXA7-GTPase. ANXA7-GTPase contains a calcium binding domain that classifies it as a member of the annexin family. The cancer-specific expression of ANXA7-GTPase, coupled with its importance in regulating cell death, cell motility, and invasion, makes it a useful diagnostic marker of cancer and a potential target for cancer treatment. Recently, emerging evidence suggests that ANXA7-GTPase is a critical factor associated with the metastatic state of several cancers and can be used as a risk biomarker for HER2 negative breast cancer patients. Cross talk between ANXA7, PTEN, and EGFR leads to constitutive activation of PI3K-AKT signaling, a central pathway of tumor cell survival and proliferation. This review focuses on the recent progress in understanding the tumor suppressor functions of ANXA7-GTPase emphasizing the role of this gene in Ca metabolism, and exploring opportunities for function as an example of a calcium binding GTPase acting as a tumor suppressor and opportunities for ANXA7-GTPase gene cancer therapy.
染色体异常，包括10号染色体的纯合缺失和杂合性丢失，在大多数人类肿瘤中普遍存在，包括前列腺癌、乳腺癌和肾癌。膜联蛋白A7 - GTP酶是一种肿瘤抑制因子，常因10q21的基因组改变而失活。在过去几年中，积累了大量数据，描述了膜联蛋白A7 - GTP酶在多种人类恶性肿瘤中的失活情况，并证明了膜联蛋白A7 - GTP酶的肿瘤抑制潜力。膜联蛋白A7 - GTP酶含有一个钙结合结构域，这使其被归类为膜联蛋白家族的成员。膜联蛋白A7 - GTP酶在癌症中的特异性表达，加上其在调节细胞死亡、细胞运动和侵袭方面的重要性，使其成为一种有用的癌症诊断标志物和癌症治疗的潜在靶点。最近，新出现的证据表明，膜联蛋白A7 - GTP酶是与几种癌症转移状态相关的关键因素，可作为HER2阴性乳腺癌患者的风险生物标志物。膜联蛋白A7、PTEN和表皮生长因子受体（EGFR）之间的相互作用导致PI3K - AKT信号通路的组成性激活，这是肿瘤细胞存活和增殖的核心途径。本综述重点关注在理解膜联蛋白A7 - GTP酶的肿瘤抑制功能方面的最新进展，强调该基因在钙代谢中的作用，并探索其作为一种作为肿瘤抑制因子的钙结合GTP酶发挥功能的机会以及膜联蛋白A7 - GTP酶基因癌症治疗的机会。
