V A Subramanian, Bairwa Ravindra Kumar, Sharma Pradeep Kumar, Bissa Bhawana
Department of Biochemistry, Central University of Rajasthan, NH-8, Bandarsindri, Kishangarh, Distt. Ajmer, Rajasthan 305817, India.
Food, Drug & Chemical Toxicology Group, CSIR-Indian Institute of Toxicology Research, Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow, Uttar Pradesh 226001, India.
Life Sci. 2022 Jul 1;300:120552. doi: 10.1016/j.lfs.2022.120552. Epub 2022 Apr 19.
"That survival instinct, that will to live, that need to get back to life again, is more powerful than any consideration of taste, decency, politeness, manners, civility, anything. It's such a powerful force." This quote by famous director Danny Boyle is a perfect analogy to describe the cancer cell's inexhaustible drive to persist against all odds. In order to adapt to a hostile environment, the cancer cells rely on multiple mechanisms including immune escape, epithelial to mesenchymal transition, angiogenesis, extravasation, autophagy, exosome release among others. Cancer cells depute their internal and external warriors, autophagosomes and exosomes, to dwell in the belligerent tumor microenvironment. It is quite reasonable for a cancer cell, striving to survive, to invest in pathways that will provide the maximum advantage. Autophagy is an important cellular degradation pathway, while the exosome pathway provides an alternative cargo disposal mechanism to maintain the homeostasis and cell survival. While autophagic degradation provides the essential nutrients to rapidly dividing cells, exosomal secretion ensures that the tumor microenvironment is attuned to accommodate the swiftly expanding tumor mass. Studies have revealed that exosomes secreted by cancer cells can modulate autophagy in recipient cells, while autophagy can influence the biogenesis of exosomes. Autophagy and exosome crosstalk is extremely complex and it is only beginning to be recognized and documented. This review is focused on discussing the roles of autophagy and exosomes in the cancer cell's adaptation to the tumor microenvironment and how the two pathways are coordinately regulated to facilitate cancer cell survival.
著名导演丹尼·博伊尔的这句话:“那种生存本能,那种活下去的意志,那种重回生活的需求,比任何关于口味、得体、礼貌、礼仪、文明等的考量都要强大得多。这是一股极其强大的力量。”恰如其分地类比了癌细胞不顾一切持续生存的无尽动力。为了适应恶劣环境,癌细胞依靠多种机制,包括免疫逃逸、上皮-间质转化、血管生成、外渗、自噬、外泌体释放等。癌细胞派遣其内部和外部的战士——自噬体和外泌体,驻扎在充满敌意的肿瘤微环境中。对于一个努力求生的癌细胞来说,投入能提供最大优势的途径是完全合理的。自噬是一种重要的细胞降解途径,而外泌体途径提供了一种替代的货物处理机制以维持体内平衡和细胞存活。自噬性降解为快速分裂的细胞提供必需营养,而外泌体分泌确保肿瘤微环境能够适应迅速扩大的肿瘤块。研究表明,癌细胞分泌的外泌体可以调节受体细胞中的自噬,而自噬可以影响外泌体的生物发生。自噬和外泌体的相互作用极其复杂,才刚刚开始被认识和记录。这篇综述重点讨论自噬和外泌体在癌细胞适应肿瘤微环境中的作用,以及这两条途径如何协同调节以促进癌细胞存活。