Role of autophagy in gastric carcinogenesis

Abstract

Gastric cancer represents a common and highly fatal malignancy, and thus a pathophysiology-based reconsideration is necessary, given the absence of efficient therapeutic regimens. In this regard, emerging data reveal a significant role of autophagy in gastric oncogenesis, progression, metastasis and chemoresistance. Although autophagy comprises a normal primordial process, ensuring cellular homeostasis under energy depletion and stress conditions, alterations at any stage of the complex regulatory system could stimulate a tumorigenic and promoting cascade. Among others, Helicobacter pylori infection induces a variety of signaling molecules modifying autophagy, during acute infection or after chronic autophagy degeneration. Subsequently, defective autophagy allows malignant transformation and upon cancer establishment, an overactive autophagy is stimulated. This overexpressed autophagy provides energy supplies and resistance mechanisms to gastric cancer cells against hosts defenses and anticancer treatment. This review interprets the implicated autophagic pathways in normal cells and in gastric cancer to illuminate the potential preventive, therapeutic and prognostic benefits of understanding and intervening autophagy.

Keywords: Gastric cancer; Autophagy; Helicobacter pylori; Chemoresistance; Prognosis

Core Tip: Autophagy comprises a substantial normal cellular function, implicated in benign and malignant diseases. Its complex regulatory system can be affected at any stage by endogenous and environmental factors. Helicobacter pylori expresses and stimulates a wide range of autophagy modulators, thus promoting or inhibiting autophagy to yield a survival benefit and cause damage. Concerning gastric cancer, the dysregulated autophagic process facilitates tumor generation, progress and resistance to chemotherapy, through various mechanisms. The current review attempts to decrypt and simplify those mechanisms and the respective pathways, to explain their promising potential for the development of therapeutic agents and prognostic tools.