Adeshakin Funmilayo O, Adeshakin Adeleye O, Afolabi Lukman O, Yan Dehong, Zhang Guizhong, Wan Xiaochun
Guangdong Immune Cell Therapy Engineering and Technology Research Center, Center for Protein and Cell-Based Drugs, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
University of Chinese Academy of Sciences, Beijing, China.
Front Oncol. 2021 Mar 29;11:626577. doi: 10.3389/fonc.2021.626577. eCollection 2021.
The attachment of cells to the extracellular matrix (ECM) is the hallmark of structure-function stability and well-being. ECM detachment in localized tumors precedes abnormal dissemination of tumor cells culminating in metastasis. Programmed cell death (PCD) is activated during tumorigenesis to clear off ECM-detached cells through "anoikis." However, cancer cells develop several mechanisms for abrogating anoikis, thus promoting their invasiveness and metastasis. Specific factors, such as growth proteins, pH, transcriptional signaling pathways, and oxidative stress, have been reported as drivers of anoikis resistance, thus enhancing cancer proliferation and metastasis. Recent studies highlighted the key contributions of metabolic pathways, enabling the cells to bypass anoikis. Therefore, understanding the mechanisms driving anoikis resistance could help to counteract tumor progression and prevent metastasis. This review elucidates the dynamics employed by cancer cells to impede anoikis, thus promoting proliferation, invasion, and metastasis. In addition, the authors have discussed other metabolic intermediates (especially amino acids and nucleotides) that are less explored, which could be crucial for anoikis resistance and metastasis.
细胞与细胞外基质（ECM）的附着是结构 - 功能稳定性和健康状态的标志。局部肿瘤中ECM的脱离先于肿瘤细胞的异常播散，最终导致转移。在肿瘤发生过程中，程序性细胞死亡（PCD）被激活，通过“失巢凋亡”清除与ECM脱离的细胞。然而，癌细胞发展出多种机制来消除失巢凋亡，从而促进其侵袭和转移。据报道，特定因素，如生长蛋白、pH值、转录信号通路和氧化应激，是失巢凋亡抗性的驱动因素，从而增强癌症的增殖和转移。最近的研究强调了代谢途径的关键作用，使细胞能够绕过失巢凋亡。因此，了解驱动失巢凋亡抗性的机制有助于对抗肿瘤进展并预防转移。本综述阐明了癌细胞用于阻碍失巢凋亡的动态过程，从而促进增殖、侵袭和转移。此外，作者还讨论了其他较少被探索的代谢中间体（尤其是氨基酸和核苷酸），它们可能对失巢凋亡抗性和转移至关重要。
