Increased ATG5 Expression Predicts Poor Prognosis and Promotes EMT in Cervical Carcinoma

Zhou, Suna; Wang, Xuequan; Ding, Jianbo; Yang, Haihua; Xie, Youyou

doi:10.3389/fcell.2021.757184

Cited by 11 publications

(8 citation statements)

References 78 publications

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“…EMT has been identified as a critical driver of embryonic development, tissue fibrosis, wound healing, tumorigenesis, and metastasis 12,32 . As previously described by many studies, patients with enriched EMT‐related gene expression are associated with a poorer prognosis in many human cancers 33–35 . In our study, the high‐risk group we identified also has the characteristics of EMT signal pathway activation and a worse prognosis, which is consistent with the previous study (Figures 3 and 4).…”

Section: Discussionsupporting

confidence: 92%

“… 12 , 32 As previously described by many studies, patients with enriched EMT‐related gene expression are associated with a poorer prognosis in many human cancers. 33 , 34 , 35 In our study, the high‐risk group we identified also has the characteristics of EMT signal pathway activation and a worse prognosis, which is consistent with the previous study (Figures 3 and 4 ). A mesenchymal subtype of GC (defined by a positive EMT signature) often showed increasing resistance to radio‐ and chemotherapeutics and poor response to ICB treatment.…”

Section: Discussionsupporting

confidence: 92%

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Five EMT‐related genes signature predicts overall survival and immune environment in microsatellite instability‐high gastric cancer

Zhang

Cao

et al. 2022

Cancer Medicine

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Background Microsatellite instability‐high (MSI‐H) subgroup of gastric cancer (GC) is characterized by a high tumor mutational burden, increased lymphocytic infiltration, and enhanced inflammatory cytokines. GC patients with MSI‐H status have a good response to immune checkpoint blockade management. However, heterogeneity within the subtype and the underlying mechanisms of shaping tumor microenvironments remain poorly understood. Methods RNA expression levels and clinical parameters of GC were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The data were analyzed using single‐sample Gene Set Enrichment Analysis (ssGSEA), univariate Cox regression, multivariate Cox regression, and Least Absolute Shrinkage Selection Operator (LASSO) regression. In addition, multiplex immunohistochemistry (mIHC) was used in our clinical cohort for the tumor microenvironment study. Results By ssGSEA and survival analysis, the EMT signaling pathway was identified as a representative pathway, which can stratify the patients with MSI‐H GC with significant survival predictive power. Then, a novel representative EMT‐related five‐gene signature (namely CALU, PCOLCE2, PLOD2, SGCD, and THBS2) was established from EMT signaling gene set, which sensitivity and specificity were further validated in the independent GEO database (GSE62254) cohort for disease outcome prediction. Based on public single‐cell data and in situ immunohistochemistry, we found that most of these five genes were abundantly expressed in cancer‐associated fibroblasts. Furthermore, patients with high or low risk divided by this five‐gene signature exhibited a strong correlation of the distinct patterns of tumor immune microenvironment. By mIHC staining of sections from 30 patients with MSI‐H status, we showed that the patients with better prognoses had the increased infiltration of CD8+ cells in the primary tumoral tissue. Conclusion Our study developed a simple five‐gene signature for stratifying MSI‐H GC patients with survival predictive power.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 92%

Five EMT‐related genes signature predicts overall survival and immune environment in microsatellite instability‐high gastric cancer

Zhang

Cao

et al. 2022

Cancer Medicine

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“…Further evidence has suggested that autophagy plays a fundamental role in the EMT in cancer [ 18 ]. Given the complex relationship between the two processes, we examined the influence of autophagy on EMT in HLE cells through two specific autophagy modulators, rapa and 3-MA.…”

Section: Discussionmentioning

confidence: 99%

TP53INP2 Contributes to TGF-β2-Induced Autophagy during the Epithelial–Mesenchymal Transition in Posterior Capsular Opacification Development

Cui

Yang

Shi

et al. 2022

Cells

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Background: Posterior capsule opacification (PCO) is the most common complication after cataract surgery, in which increased levels of transforming growth factor-beta 2 (TGF-β2) accelerate PCO formation; however, the pathological mechanisms are not fully understood. This study aims to explore the regulation mechanism of TGF-β2 in PCO formation via its autophagic functions. Methods: The autophagic effect of TGF-β2 was detected by transmission electron microscopy (TEM), Western blotting, and immunofluorescence analysis. The association between autophagy and the epithelial–mesenchymal transition (EMT) was evaluated by qPCR and Western blotting. The transcriptome analysis was used to uncover the molecular mechanism of TGF-β2-induced PCO formation. Results: TGF-β2 specifically promotes autophagy flux in human lens epithelial cells. The activation of autophagy by rapamycin can promote EMT marker synthesis and improve cell migration. However, the inhibition of autophagy by 3-MA attenuates EMT. To uncover the molecular mechanisms, we performed RNA sequencing and found that TGF-β2 elevated tumor protein p53-inducible nuclear protein2 (TP53INP2) expression, which was accompanied by a nuclear-to-cytoplasm translocation. Moreover, the knockdown of TP53INP2 blocked the TGF-β2-induced autophagy and EMT processes, revealing that TP53INP2 plays an important role in TGF-β2-induced autophagy during EMT. Conclusions: Taken together, the results of this study suggested that TP53INP2 was a novel regulator of PCO development by TGF-β2, and notably, TP53INP2, may be a potential target for the pharmacological treatment of PCO.

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“…The majority of the tumors activate the epithelial-mesenchymal transition (EMT) program to attain the stem cell-like properties and to promote their growth, invasion, and metastasis. The autophagy-related genes, especially ATG5 play a critical role in the EMT process as indicated by a study on cervical cancer cells ( 119 ). In radio-resistant cancer cells, like pancreatic ductal adenocarcinoma cells and NSCLC stem cells, autophagy has found to be essential in promoting tumor growth and invasiveness ( 120 ) as well as maintaining the stem cell-like properties ( 121 ) of the cells.…”

Section: Influence Of Autophagy On Radiation Response Of Tumorsmentioning

confidence: 99%

Role of autophagy in tumor response to radiation: Implications for improving radiotherapy

Roy¹,

Bera

Saso

et al. 2022

Front. Oncol.

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Autophagy is an evolutionary conserved, lysosome-involved cellular process that facilitates the recycling of damaged macromolecules, cellular structures, and organelles, thereby generating precursors for macromolecular biosynthesis through the salvage pathway. It plays an important role in mediating biological responses toward various stress, including those caused by ionizing radiation at the cellular, tissue, and systemic levels thereby implying an instrumental role in shaping the tumor responses to radiotherapy. While a successful execution of autophagy appears to facilitate cell survival, abortive or interruptions in the completion of autophagy drive cell death in a context-dependent manner. Pre-clinical studies establishing its ubiquitous role in cells and tissues, and the systemic response to focal irradiation of tumors have prompted the initiation of clinical trials using pharmacologic modifiers of autophagy for enhancing the efficacy of radiotherapy. However, the outcome from the Phase I/II trials in many human malignancies has so far been equivocal. Such observations have not only precluded the advancement of these autophagy modifiers in the Phase III trial but have also raised concerns regarding their introduction as an adjuvant to radiotherapy. This warrants a thorough understanding of the biology of the cancer cells, including its spatio-temporal context, as well as its microenvironment all of which might be the crucial factors that determine the success of an autophagy modifier as an anticancer agent. This review captures the current understanding of the interplay between radiation induced autophagy and the biological responses to radiation damage as well as provides insight into the potentials and limitations of targeting autophagy for improving the radiotherapy of tumors.

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Increased ATG5 Expression Predicts Poor Prognosis and Promotes EMT in Cervical Carcinoma

Cited by 11 publications

References 78 publications

Five EMT‐related genes signature predicts overall survival and immune environment in microsatellite instability‐high gastric cancer

Five EMT‐related genes signature predicts overall survival and immune environment in microsatellite instability‐high gastric cancer

TP53INP2 Contributes to TGF-β2-Induced Autophagy during the Epithelial–Mesenchymal Transition in Posterior Capsular Opacification Development

Role of autophagy in tumor response to radiation: Implications for improving radiotherapy

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