Rheb has found to be expressed in prostate cancer and could promote tumourigenesis with PTEN haplo-insufficiency [16]. 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 double-membrane 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 [2C4]. Open in a separate window Fig. 1 Title: An overview of the central autophagy mechanism. The ULK and Beclin 1 TIC10 isomer protein complexes initiate phagophore formation. Atg5/12/16 and LC3-II are responsible for expansion to autophagosome. Fusion of autophagosome and lysosome produces autolysosome as the final process. Legend: Green arrows represent activating processes for autophagy TIC10 isomer stimulation and the red arrow represents a repressing process for autophagy inhibition 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 (50C70%) 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 Beclin-1 could favour the development of cancer. For colorectal and gastric cancers, associations were found with the down-regulation of Bif-1 and Atg2B, Atg5, Atg9B and Atg12 mutations, which led to inhibition of programmed cell death in colon cancer (Fig.?1). Also, mutation of exon 8 of UV radiation resistance-associated gene (UVRAG) reduced autophagy and promoted these cancer types [2, 4]. Taken together, there is broad evidence that autophagy and ATG type of proteins have a tumour suppressive role and down-regulation of the latter can promote tumourigenesis in early stage tumours. Apart from direct suppression of tumourigenesis, autophagy could also induce cellular senescence, which is a state of stable cell cycle arrest that protect the cells against a variety of cellular insults. It is a delayed stress response with multiple effector mechanisms including oncogene-induced senescence. Oncogene initially induces a highly proliferative state in cells. However, senescence will gradually replace the mitotic burst state and this illustrates its tumour suppressing role. A past study has demonstrated that the autophagy marker microtubule-associated protein 1 light chain 3 (MAP1LC3) was up-regulated in Ras oncogene-induced senescence and resulted in the accumulation of ARHGEF11 autophagosomes in these cells [7]. The lack of Atg5 or Atg7 could also diminish oncogene-induced senescence and delay the production of senescence-associated cytokine [4]. These pieces of evidence support the notion that senescence may be promoted by autophagy and basal TIC10 isomer autophagy is important in restricting proliferation during oncogenic stress. In addition, combining autophagy activation by rapamycin and irradiation could initiate premature senescence in both in vitro and in vivo models of radiation-resistant glioblastoma and parotid carcinoma cells. In the in vitro model, irradiation increases autophagic flux for 72 h and the addition of rapamycin.