Anoikis resistance in Cancer: Mechanisms, therapeutic strategies, potential targets, and models for enhanced understanding

IF 9.1 1区医学 Q1 ONCOLOGY

Cancer letters Pub Date : 2025-04-26 DOI:10.1016/j.canlet.2025.217750

Pallab Shaw , Arpan Dey Bhowmik , Mohan Shankar Gopinatha Pillai , Nathan Robbins , Shailendra Kumar Dhar Dwivedi , Geeta Rao

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引用次数: 0

Abstract

Anoikis, defined as programmed cell death triggered by the loss of cell-extracellular matrix (ECM) and cell-cell interactions, is crucial for maintaining tissue homeostasis and preventing aberrant cell migration. Cancer cells, however, display anoikis resistance (AR) which in turn enables cancer metastasis. AR results from alterations in apoptotic signaling, metabolic reprogramming, autophagy modulation, and epigenetic changes, allowing cancer cells to survive in detached conditions. In this review we describe the mechanisms underlying both anoikis and AR, focusing on intrinsic and extrinsic pathways, disrupted cell-ECM interactions, and autophagy in cancer. Recent findings (i.e., between 2014 and 2024) on epigenetic regulation of AR and its role in metastasis are discussed. Therapeutic strategies targeting AR, including chemical inhibitors, are highlighted alongside a network analysis of 122 proteins reported to be associated with AR which identifies 53 hub proteins as potential targets. We also evaluate in vitro and in vivo models for studying AR, emphasizing their role in advancing metastasis research. Our overall goal is to guide future studies and therapeutic developments to counter cancer metastasis.

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癌症中的Anoikis耐药：机制、治疗策略、潜在靶点和增强理解的模型

失活被定义为由细胞外基质（ECM）和细胞间相互作用丧失引发的程序性细胞死亡，对于维持组织稳态和防止异常细胞迁移至关重要。然而，癌细胞表现出anoikis抗性（AR），这反过来又使癌症转移。AR由凋亡信号、代谢重编程、自噬调节和表观遗传改变的改变引起，使癌细胞在分离条件下存活。在这篇综述中，我们描述了anoikis和AR的机制，重点是内在和外在途径，破坏细胞- ecm相互作用，以及癌症中的自噬。本文讨论了近年来（即2014年至2024年）关于AR的表观遗传调控及其在转移中的作用。针对AR的治疗策略，包括化学抑制剂，以及对122种与AR相关的蛋白质的网络分析，其中确定了53种枢纽蛋白作为潜在靶点。我们还评估了研究AR的体外和体内模型，强调了它们在推进转移研究中的作用。我们的总体目标是指导未来的研究和治疗发展，以对抗癌症转移。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer letters 医学-肿瘤学

CiteScore

17.70

自引率

2.10%

发文量

427

审稿时长

15 days

期刊介绍： Cancer Letters is a reputable international journal that serves as a platform for significant and original contributions in cancer research. The journal welcomes both full-length articles and Mini Reviews in the wide-ranging field of basic and translational oncology. Furthermore, it frequently presents Special Issues that shed light on current and topical areas in cancer research. Cancer Letters is highly interested in various fundamental aspects that can cater to a diverse readership. These areas include the molecular genetics and cell biology of cancer, radiation biology, molecular pathology, hormones and cancer, viral oncology, metastasis, and chemoprevention. The journal actively focuses on experimental therapeutics, particularly the advancement of targeted therapies for personalized cancer medicine, such as metronomic chemotherapy. By publishing groundbreaking research and promoting advancements in cancer treatments, Cancer Letters aims to actively contribute to the fight against cancer and the improvement of patient outcomes.