Programmed cell death pathways in cancer: a review of apoptosis, autophagy and programmed necrosis

Abstract

Programmed cell death (PCD), referring to apoptosis, autophagy and programmed necrosis, is proposed to be death of a cell in any pathological format, when mediated by an intracellular program. These three forms of PCD may jointly decide the fate of cells of malignant neoplasms; apoptosis and programmed necrosis invariably contribute to cell death, whereas autophagy can play either pro-survival or pro-death roles. Recent bulk of accumulating evidence has contributed to a wealth of knowledge facilitating better understanding of cancer initiation and progression with the three distinctive types of cell death. To be able to decipher PCD signalling pathways may aid development of new targeted anti-cancer therapeutic strategies. Thus in this review, we present a brief outline of apoptosis, autophagy and programmed necrosis pathways and apoptosis-related microRNA regulation, in cancer. Taken together, understanding PCD and the complex interplay between apoptosis, autophagy and programmed necrosis may ultimately allow scientists and clinicians to harness the three types of PCD for discovery of further novel drug targets, in the future cancer treatment.

Apoptotic Mediators are Upregulated in the Skeletal Muscle of Chronic/Progressive Mouse Model of Parkinson's Disease

“…Apoptosis is a programmed cell death that is mediated by a family of cysteine proteases called caspases (Sinkovics, 1991;Elmore, 2007;Ouyang et al, 2012). Caspases exist in the cell as inactive zymogens, which are activated in response to apoptotic stimuli (Shi, 2004).…”

Cellular senescence and autophagy of myoepithelial cells are involved in the progression of in situ areas of carcinoma ex-pleomorphic adenoma to invasive carcinoma. An in vitro model

“…This process is characterized by specific morphological and biochemical changes in the dying cells (Ouyang et al 2012). Among the central regulators of apoptosis are the Bcl-2 family, which includes both pro-(Bax, Bak, Bad) and antiapoptotic regulators (Bcl-2, Bcl-xl, Mcl-1) (Placzek et al 2010), as well as inhibitors of apoptosis (IAPs), including Survivin, NIAP, XIAP and c-IAP (Plati et al 2011;Ulukaya et al 2011;Cheung et al 2011).…”

T-cell development of resistance to apoptosis is driven by a metabolic shift in carbon source and altered activation of death pathways

“…However, in various human disease states, including neurodegeneration, autoimmunity, and cancer, a deregulation or malfunction of this inherent program occurs and cells may develop resistance to apoptosis. 5,6 Apoptosis occurs through two main signaling pathways: an extrinsic pathway that utilizes a diversified group of cell surface death receptors; [7][8][9][10][11][12][13][14] and an intrinsic pathway that utilizes various intracellular organelles to execute the programmed cell death machinery. [15][16][17][18][19][20] An important and well-studied point of control for both the extrinsic and intrinsic apoptotic pathways is the Bcl-2 family of proteins that comprise both pro-and antiapoptotic members and regulate the apoptotic program through a tightly controlled series of checks and balances.…”