Rahman Md Ataur, Park Moon Nyeo, Rahman Md Hasanur, Rashid Md Mamunur, Islam Rokibul, Uddin Md Jamal, Hannan Md Abdul, Kim Bonglee
Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul, South Korea.
Korean Medicine-Based Drug Repositioning Cancer Research Center, College of Korean Medicine, Kyung Hee University, Seoul, South Korea.
Front Cell Dev Biol. 2022 Jan 26;10:761080. doi: 10.3389/fcell.2022.761080. eCollection 2022.
The key tumor suppressor protein p53, additionally known as p53, represents an attractive target for the development and management of anti-cancer therapies. p53 has been implicated as a tumor suppressor protein that has multiple aspects of biological function comprising energy metabolism, cell cycle arrest, apoptosis, growth and differentiation, senescence, oxidative stress, angiogenesis, and cancer biology. Autophagy, a cellular self-defense system, is an evolutionarily conserved catabolic process involved in various physiological processes that maintain cellular homeostasis. Numerous studies have found that p53 modulates autophagy, although the relationship between p53 and autophagy is relatively complex and not well understood. Recently, several experimental studies have been reported that p53 can act both an inhibitor and an activator of autophagy which depend on its cellular localization as well as its mode of action. Emerging evidences have been suggested that the dual role of p53 which suppresses and stimulates autophagy in various cencer cells. It has been found that p53 suppression and activation are important to modulate autophagy for tumor promotion and cancer treatment. On the other hand, activation of autophagy by p53 has been recommended as a protective function of p53. Therefore, elucidation of the new functions of p53 and autophagy could contribute to the development of novel therapeutic approaches in cancer biology. However, the underlying molecular mechanisms of p53 and autophagy shows reciprocal functional interaction that is a major importance for cancer treatment and manegement. Additionally, several synthetic drugs and phytochemicals have been targeted to modulate p53 signaling via regulation of autophagy pathway in cancer cells. This review emphasizes the current perspectives and the role of p53 as the main regulator of autophagy-mediated novel therapeutic approaches against cancer treatment and managements.
关键肿瘤抑制蛋白p53，也被称为p53，是抗癌疗法开发与管理的一个有吸引力的靶点。p53作为一种肿瘤抑制蛋白，具有多种生物学功能，包括能量代谢、细胞周期阻滞、凋亡、生长与分化、衰老、氧化应激、血管生成以及癌症生物学等方面。自噬是一种细胞自我防御系统，是一种进化上保守的分解代谢过程，参与维持细胞内稳态的各种生理过程。大量研究发现p53可调节自噬，尽管p53与自噬之间的关系相对复杂且尚未完全理解。最近，有几项实验研究报道，p53既可以作为自噬的抑制剂，也可以作为自噬的激活剂，这取决于其细胞定位及其作用方式。新出现的证据表明，p53在各种癌细胞中具有抑制和刺激自噬的双重作用。已经发现p53的抑制和激活对于调节自噬以促进肿瘤生长和癌症治疗很重要。另一方面，p53激活自噬被认为是p53的一种保护功能。因此，阐明p53和自噬的新功能可能有助于癌症生物学中新型治疗方法的开发。然而，p53和自噬的潜在分子机制显示出相互的功能相互作用，这对癌症治疗和管理至关重要。此外，几种合成药物和植物化学物质已被靶向通过调节癌细胞中的自噬途径来调节p53信号传导。本综述强调了当前的观点以及p53作为自噬介导的抗癌治疗和管理新治疗方法的主要调节因子的作用。
