Manzoor Shaista, Muhammad Jibran Sualeh, Maghazachi Azzam A, Hamid Qutayba
Department of Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.
Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.
Front Oncol. 2022 Jul 14;12:924290. doi: 10.3389/fonc.2022.924290. eCollection 2022.
Colorectal cancer (CRC) is among the topmost malignancies for both genders. Despite the high incidence rate and advances in diagnostic tools, treatment in many cases is still ineffective. Most cancerous lesions in CRC begin as benign, followed by the development of invasive forms and metastases. The development of CRC has been linked to defects in autophagy, which plays both a pro-and anti-tumor role and is mainly context-dependent. Autophagy suppression could enhance apoptosis p53 activation, or autophagy also promotes tumor progression by maintaining tumor growth and increasing resistance to chemotherapy. Autophagy promotes the invasion and metastasis of CRC cells increased epithelial-mesenchymal transition (EMT). Moreover, dysbiosis of gut microbiota upregulated autophagy and metastasis markers. Autophagy responses may also modulate the tumor microenvironment (TME) regulating the differentiation process of several innate immune cells. Treatments that promote tumor cell death by stimulating or inhibiting autophagy could be beneficial if used as an adjunct treatment, but the precise role of various autophagy-modulating drugs in CRC patients is needed to be explored. In this article, we present an overview of the autophagy process and its role in the pathogenesis and therapeutic resistance of CRC. Also, we focused on the current understanding of the role of the EMT and TME, including its relation to gut microbiota and immune cells, in autophagic manipulation of CRC. We believe that there is a potential link between autophagy, TME, EMT, and drug resistance, suggesting that further studies are needed to explore this aspect.
结直肠癌（CRC）是男女中最常见的恶性肿瘤之一。尽管发病率高且诊断工具有所进步，但在许多情况下治疗仍然无效。CRC中的大多数癌性病变开始时是良性的，随后发展为侵袭性形式和转移。CRC的发生与自噬缺陷有关，自噬既具有促肿瘤作用又具有抗肿瘤作用，且主要取决于具体情况。自噬抑制可增强凋亡、p53激活，或者自噬也通过维持肿瘤生长和增加对化疗的抗性来促进肿瘤进展。自噬促进CRC细胞的侵袭和转移，增加上皮-间质转化（EMT）。此外，肠道微生物群失调会上调自噬和转移标志物。自噬反应还可能通过调节几种先天免疫细胞的分化过程来调节肿瘤微环境（TME）。通过刺激或抑制自噬来促进肿瘤细胞死亡的治疗方法作为辅助治疗可能有益，但需要探索各种自噬调节药物在CRC患者中的精确作用。在本文中，我们概述了自噬过程及其在CRC发病机制和治疗抗性中的作用。此外，我们重点关注了目前对EMT和TME的作用的理解，包括其与肠道微生物群和免疫细胞的关系，以及在CRC自噬调控中的作用。我们认为自噬、TME、EMT和耐药性之间存在潜在联系，这表明需要进一步研究来探索这一方面。
