Adult Cancer Program, Sarcoma and Nano-Oncology Research Group, Faculty of Medicine, Lowy Cancer Research Centre, Prince of Wales Clinical School, University of New South Wales, Room 209, Sydney, NSW, 2052, Australia.
J Cancer Res Clin Oncol. 2013 Nov;139(11):1795-805. doi: 10.1007/s00432-013-1482-5. Epub 2013 Aug 4.
Anoikis ('homelessness' in Greek) is a form of apoptosis following the detachment of cells from the appropriate extracellular matrix (Chiarugi and Giannoni in Biochem Pharmacol 76:1352-1364, 2008). Resistance to anoikis is a critical mediator of metastasis in cancer by enabling cancer cells to survive during invasion and transport in the blood and lymph. Numerous regulators and mechanisms of anoikis in human cancer have been proposed to date. Consequently, the identification of key regulators of anoikis that can be targeted to at least partially restore anoikis sensitivity in cancer cells is important in the development of therapies to treat metastatic cancer.
A literature search focusing on the regulators of anoikis in human cancer was performed on the Medline, Embase and Scopus databases.
Mcl-1, Cav-1, Bcl-(xL), cFLIP, 14-3-3ζ and Bit1 appear to regulate anoikis in human cancer by participating in the intrinsic apoptotic pathway, extrinsic apoptotic pathway or caspase-independent pathways. Mcl-1, Cav-1, Bcl-(xL), cFLIP and 14-3-3ζ are suppressors of anoikis, and their upregulation confers anoikis resistance to cancer cells. Bit1 is a promoter of anoikis and is downregulated to confer anoikis resistance in metastatic cancer.
Anoikis is a complex process involving the crosstalk between different signalling pathways. The dysregulated expression of key regulators of anoikis that participate in these signalling pathways promotes anoikis resistance in human cancer. These regulators of anoikis might therefore be the targets for developing therapies to overcome anoikis resistance in metastatic cancer.
细胞凋亡（希腊语意为“无家可归”）是细胞从适当的细胞外基质上脱离后发生的一种凋亡形式（Chiarugi 和 Giannoni 在 Biochem Pharmacol 76:1352-1364, 2008）。细胞对细胞凋亡的抵抗是癌症转移的一个关键介质，使癌细胞能够在入侵和血液及淋巴运输过程中存活。迄今为止，已经提出了许多人类癌症中细胞凋亡的调节因子和机制。因此，鉴定可以靶向的细胞凋亡的关键调节因子，至少部分恢复癌细胞的细胞凋亡敏感性，对于开发治疗转移性癌症的疗法非常重要。
在 Medline、Embase 和 Scopus 数据库上进行了一项针对人类癌症中细胞凋亡调节因子的文献检索。
Mcl-1、Cav-1、Bcl-(xL)、cFLIP、14-3-3ζ 和 Bit1 似乎通过参与内在凋亡途径、外在凋亡途径或 caspase 非依赖性途径来调节人类癌症中的细胞凋亡。Mcl-1、Cav-1、Bcl-(xL)、cFLIP 和 14-3-3ζ 是细胞凋亡的抑制剂，其上调赋予癌细胞对细胞凋亡的抵抗性。Bit1 是细胞凋亡的促进剂，其下调赋予转移性癌症对细胞凋亡的抵抗性。
细胞凋亡是一个涉及不同信号通路相互作用的复杂过程。参与这些信号通路的细胞凋亡关键调节因子的失调表达促进了人类癌症中细胞凋亡的抵抗性。因此，这些细胞凋亡的调节因子可能是开发克服转移性癌症中细胞凋亡抵抗性的治疗方法的靶点。
