Department of Surgery, Medicine, Dentistry and Morphological Sciences with Interest in Transplant, Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Via del Pozzo, 71-41124 Modena, Italy.
Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Via del Pozzo, 71-41124 Modena, Italy.
Int J Mol Sci. 2023 Jun 15;24(12):10201. doi: 10.3390/ijms241210201.
Colorectal cancer (CRC) remains a major life-threatening malignancy, despite numerous therapeutic and screening attempts. Apoptosis and autophagy are two processes that share common signaling pathways, are linked by functional relationships and have similar protein components. During the development of cancer, the two processes can trigger simultaneously in the same cell, causing, in some cases, an inhibition of autophagy by apoptosis or apoptosis by autophagy. Malignant cells that have accumulated genetic alterations can take advantage of any alterations in the apoptotic process and as a result, progress easily in the cancerous transformation. Autophagy often plays a suppressive role during the initial stages of carcinogenicity, while in the later stages of cancer development it can play a promoting role. It is extremely important to determine the regulation of this duality of autophagy in the development of CRC and to identify the molecules involved, as well as the signals and the mechanisms behind it. All the reported experimental results indicate that, while the antagonistic effects of autophagy and apoptosis occur in an adverse environment characterized by deprivation of oxygen and nutrients, leading to the formation and development of CRC, the effects of promotion and collaboration usually involve an auxiliary role of autophagy compared to apoptosis. In this review, we elucidate the different roles of autophagy and apoptosis in human CRC development.
结直肠癌(CRC)尽管进行了许多治疗和筛查尝试,但仍然是一种严重威胁生命的恶性肿瘤。细胞凋亡和自噬是两个共享共同信号通路、通过功能关系相互关联且具有相似蛋白成分的过程。在癌症的发展过程中,这两个过程可以在同一细胞中同时触发,在某些情况下,自噬会被细胞凋亡抑制,或者细胞凋亡被自噬抑制。积累了遗传改变的恶性细胞可以利用细胞凋亡过程中的任何改变,因此很容易在癌变过程中进展。自噬通常在致癌性的初始阶段发挥抑制作用,而在癌症发展的后期阶段,它可以发挥促进作用。确定自噬在 CRC 发展中的这种双重性的调节以及鉴定涉及的分子以及背后的信号和机制非常重要。所有报道的实验结果表明,虽然自噬和细胞凋亡的拮抗作用发生在以缺氧和营养剥夺为特征的不利环境中,导致 CRC 的形成和发展,但促进和协作的作用通常涉及自噬相对于细胞凋亡的辅助作用。在这篇综述中,我们阐明了自噬和细胞凋亡在人类 CRC 发展中的不同作用。