Influence of autophagy on the efficacy of radiotherapy
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REVIEW
Open Access
Influence of autophagy on the efficacy of radiotherapy Shing Yau Tam, Vincent Wing Cheung Wu and Helen Ka Wai Law*
Abstract Autophagy is an important catabolic process in which cells digest and recycle their own cytoplasmic contents for maintaining cellular homeostasis. Interestingly, autophagy could play both pro-death and pro-survival roles in influencing the development of cancer via various signal pathways. As radiotherapy is one of the main treatment modalities for cancer, we reviewed the effect of autophagy modulations on radiosensitivity and radiotherapy efficacy in various cancer types. The future development of autophagy modifications for improving radiotherapy efficacy and cancer prognosis will also be discussed. Keyword: Autophagy, Radiotherapy, Signalling pathway, Radiotherapy efficacy, Radiosensitivity, Cancer Cell lines
Background Autophagy, a word derived from Greek “auto” (self ) and “phagos” (to eat), is a catabolic process in which the cells digest and recycle their own cytoplasmic contents. This critical process is evolutionarily conserved from unicellular organisms to humans and continuously occurs at basal level to ensure healthy cellular homeostasis by eliminating waste and long-lived or damaged cellular constituents. There are three types of autophagy, including macroautophagy, microautophagy and chaperonemediated autophagy [1]. Macroautophagy (hereby referred to as autophagy) is the major autophagy pathway to be discussed in this review. The process is controlled by 36 highly conserved genes which are known as AuTophaGy genes (ATGs) and starts with doublemembrane vesicles called autophagosomes, which would fuse with lysosomes to degrade cytoplasmic contents back to their original constituents by hydrolytic enzymes (Fig. 1). Different stimuli including aggregated or misfolded proteins, stress, pathogens, cytokines, starvation and protein synthesis inhibition might induce autophagy. Apart from maintaining cellular homeostasis, autophagy (or autophagy defects), may lead to several pathological conditions, including cancer [2–4].
* Correspondence: [email protected] Department of Health Technology and Informatics, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hong Kong, China
Relation of autophagy to cancer Autophagy plays an important role in cancer because of its tumour suppressing and tumour protecting function. For tumour suppressing function at the initiation stage, ATG Beclin-1 (Fig. 1) was identified as a tumour suppressor gene as it is mono-allelically deleted in many cases including ovarian cancers (75%), breast cancers (50–70%) and prostate cancers (40%) [5]. Also, Beclin-1 is allelically deleted and weakly expressed in most human breast carcinoma cell lines while the normal epithelium cells demonstrated a much higher expression [6]. In addition, overexpression of Beclin-1 in human breast carcinoma cell line MCF-7 cells could reduce tumourigenesis by inhibiting cell proliferation in a xenograft model [2]. Thus, low expression of
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