title: Autophagy promotes the survival and development of tumors by participating in the formation of vasculogenic mimicry.
abstract: Autophagy, type II nonapoptotic cell death, is characterized by the formation of double-membrane cytosolic vesicles, the recycling of damaged cytoplasmic content and the maintenance of genetic stability and cellular homeostasis, under conditions of nutrient starvation, hypoxia or other therapeutic stress. In the present study, we comprehensively discuss its indispensable role in the formation of vasculogenic mimicry (VM), capillary-like tubes consisting of cells from the tumor itself instead of vascular endothelial cells. A short hairpin RNA (shRNA) to silence beclin1, an autophagy-specific gene, was designed, synthesized and subcloned into a vector to establish an autophagy-inhibited group, while negative control and blank groups were also established using human gastric cancer SGC7901 cells. We then investigated the VM formation ability of these three groups and detected changes in gene expression, survival and invasion correspondingly. The results showed that, following the formation of VM, the expression of pluripotent genes (c-myc, oct3/4, sox-2) and autophagy-specific genes (beclin1, ATG5, ATG7) were increased, which was consistent with the negative control cell group. However, the autophagy inhibited cell group did not form VM, and the expression of pluripotent genes was decreased. Moreover, the inhibition of autophagy reduced the survival and invasive ability of cancer cells under stress. We suggest that during the formation of VM, the stable expression of genes and the maintenance of survival and invasion are indispensable. Under a stress environment, autophagy is activated to maintain the stability of gene expression, maintain survival and invasive ability and facilitate VM formation, which can provide nutrients, oxygen and invasive channels to tumors, facilitating survival and development under stress.
authors.affiliation: Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Suzhou University, Suzhou, Jiangsu 225000, P.R. China.
authors.forename: Yun-Peng
authors.initials: YP
authors.lastname: Ding
authors.affiliation: Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Suzhou University, Suzhou, Jiangsu 225000, P.R. China.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Yang
authors.affiliation: Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Suzhou University, Suzhou, Jiangsu 225000, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Suzhou University, Suzhou, Jiangsu 225000, P.R. China.
authors.forename: Chun-Gen
authors.initials: CG
authors.lastname: Xing
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D001343:Autophagy; D000071187:Autophagy-Related Protein 5; D000071193:Autophagy-Related Protein 7; D000071186:Beclin-1; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis; D009361:Neoplasm Invasiveness / Q000235:genetics*; D009389:Neovascularization, Pathologic / Q000235:genetics*; D050814:Octamer Transcription Factor-3 / Q000096:biosynthesis; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D034622:RNA Interference; D034741:RNA, Small Interfering; D055748:SOXB1 Transcription Factors / Q000096:biosynthesis; D013274:Stomach Neoplasms / Q000098:blood supply* / Q000235:genetics / Q000473:pathology; D044764:Ubiquitin-Activating Enzymes / Q000096:biosynthesis
chemical_list: C502778:ATG5 protein, human; D051017:Apoptosis Regulatory Proteins; D000071187:Autophagy-Related Protein 5; C491997:BECN1 protein, human; D000071186:Beclin-1; C489427:MYC protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D016271:Proto-Oncogene Proteins c-myc; D034741:RNA, Small Interfering; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; C509349:ATG7 protein, human; D000071193:Autophagy-Related Protein 7; D044764:Ubiquitin-Activating Enzymes