Crosstalk between autophagy and microbiota in cancer progression

Abstract

Autophagy is a highly conserved catabolic process seen in eukaryotes and is essentially a lysosome-dependent protein degradation pathway. The dysregulation of autophagy is often associated with the pathogenesis of numerous types of cancers, and can not only promote the survival of cancer but also trigger the tumor cell death. During cancer development, the microbial community might predispose cells to tumorigenesis by promoting mucosal inflammation, causing systemic disorders, and may also regulate the immune response to cancer. The complex relationship between autophagy and microorganisms can protect the body by activating the immune system. In addition, autophagy and microorganisms can crosstalk with each other in multifaceted ways to influence various physiological and pathological responses involved in cancer progression. Various molecular mechanisms, correlating the microbiota disorders and autophagy activation, control the outcomes of protumor or antitumor responses, which depend on the cancer type, tumor microenvironment and disease stage. In this review, we mainly emphasize the leading role of autophagy during the interaction between pathogenic microorganisms and human cancers and investigate the various molecular mechanisms by which autophagy modulates such complicated biological processes. Moreover, we also highlight the possibility of curing cancers with multiple molecular agents targeting the microbiota/autophagy axis. Finally, we summarize the emerging clinical trials investigating the therapeutic potential of targeting either autophagy or microbiota as anticancer strategies, although the crosstalk between them has not been explored thoroughly.

Keywords: Autophagy; Cancer progression; Microbiota; Target therapy.

Fig. 1

Overview of the mechanisms by which bacteria regulate tumor progression. Pathogenic bacteria mainly come from oral and gastrointestinal flora. Different kinds of bacteria can promote the occurrence, development and metastasis of tumors by causing host adaptive immune responses, cell cycle arrest, DNA transcription changes and DNA damage, reactive oxygen species accumulation and the activation of various signaling pathways, such as Wnt/β-catenin, NF-κB, and STAT3 signaling

Fig. 2

Different proteins or small molecules regulate autophagy pathways. Autophagy is a key regulator during tumorigenesis. It can not only promote cancer by providing nutrition for tumor cells but can also inhibit cancer progression by increasing apoptosis. Autophagy can be divided into four parts: initiation, elongation, maturation, and the fusion of autophagosomes and lysosomes. ATGs participate in each step and eventually promote or inhibit cancer

Fig. 3

Crosstalk between autophagy and microbiota in cancer. The crosstalk between autophagy and microbiota regulates multiple physiological and pathological responses, including cancer progression. Autophagy can play a role in microbiota-mediated tumorigenesis, metastasis and drug resistance in different cancers. H. pylori regulates miR-543, miR-125b-5p and autophagy through its virulence factor CagA to promote tumor occurrence. F. nucleatum mainly regulates autophagy through TLR/MyD88 and its downstream miRNA-18a^*/4802 and then plays a cancer-promoting role in colorectal cancer. P. gingivalis can induce G1 cell cycle arrest. C. jejuni can enhance cell radiosensitivity by producing cytolethal distending toxin (CDT). S. typhimurium inhibits tumor cell survival through autophagy