期刊
BIOCHEMICAL PHARMACOLOGY
卷 147, 期 -, 页码 170-182出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bcp.2017.11.021
关键词
Cell death; Autophagy modulation; Cancer metabolism; Chemotherapeutic sensitization; Mitochondria; Apoptosis
资金
- South African National Research Foundation (NRF)
- South African Medical Research Council (SAMRC)
- Cancer Association of South Africa (CANSA)
- Department of Science and Technology, New Delhi, Government of India [DST/INDO/SOUTH AFRICA/P-12/2014]
Autophagy is a major protein degradation pathway capable of upholding cellular metabolism under nutrient limiting conditions, making it a valuable resource to highly proliferating tumour cells. Although the regulatory machinery of the autophagic pathway has been well characterized, accurate modulation of this pathway remains complex in the context of clinical translatability for improved cancer therapies. In particular, the dynamic relationship between the rate of protein degradation through autophagy, i.e. autophagic flux, and the susceptibility of tumours to undergo apoptosis remains largely unclear. Adding to inefficient clinical translation is the lack of measurement techniques that accurately depict autophagic flux. Paradoxically, both increased autophagic flux as well as autophagy inhibition have been shown to sensitize cancer cells to undergo cell death, indicating the highly context dependent nature of this pathway. In this article, we aim to disentangle the role of autophagy modulation in tumour suppression by assessing existing literature in the context of autophagic flux and cellular metabolism at the interface of mitochondrial function. We highlight the urgency to not only assess autophagic flux more accurately, but also to center autophagy manipulation within the unique and inherent metabolic properties of cancer cells. Lastly, we discuss the challenges faced when targeting autophagy in the clinical setting. In doing so, it is hoped that a better understanding of autophagy in cancer therapy is revealed in order to overcome tumour chemoresistance through more controlled autophagy modulation in the future. (C) 2017 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据