Autophagy and EMT in cancer and metastasis: Who controls whom?

Gundamaraju, Rohit; Lu, Wenying; Paul, Manash K.; Jha, Niraj Kumar; Gupta, Piyush Kumar; Ojha, Shreesh; Chattopadhyay, Indranil; Rao, Pasupuleti Visweswara; Ghavami, Saeid

doi:10.1016/j.bbadis.2022.166431

Cited by 56 publications

(29 citation statements)

References 129 publications

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“…Autophagy plays a major role in many diseases, including immune diseases [ 35 , 36 ], neurodegenerative diseases [ 37 ], atherosclerosis [ 38 ], and cancers [ 39 , 40 ]. Our present work suggests that autophagy may also have a role in eosinophilic asthma.…”

Section: Discussionmentioning

confidence: 99%

Autophagy Protects against Eosinophil Cytolysis and Release of DNA

Esnault

Fichtinger

Barretto

et al. 2022

Cells

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The presence of eosinophils in the airway is associated with asthma severity and risk of exacerbations. Eosinophils deposit their damaging products in airway tissue, likely by degranulation and cytolysis. We previously showed that priming blood eosinophils with IL3 strongly increased their cytolysis on aggregated IgG. Conversely, IL5 priming did not result in significant eosinophil cytolysis in the same condition. Therefore, to identify critical events protecting eosinophils from cell cytolysis, we examined the differential intracellular events between IL5- and IL3-primed eosinophils interacting with IgG. We showed that both IL3 and IL5 priming increased the eosinophil adhesion to IgG, phosphorylation of p38, and production of reactive oxygen species (ROS), and decreased the phosphorylation of cofilin. However, autophagic flux as measured by the quantification of SQSTM1-p62 and lipidated-MAP1L3CB over time on IgG, with or without bafilomycin-A1, was higher in IL5-primed compared to IL3-primed eosinophils. In addition, treatment with bafilomycin-A1, an inhibitor of granule acidification and autophagolysosome formation, enhanced eosinophil cytolysis and DNA trap formation in IL5-primed eosinophils. Therefore, this study suggests that increased autophagy in eosinophils protects from cytolysis and the release of DNA, and thus limits the discharge of damaging intracellular eosinophilic contents.

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Section: Discussionmentioning

confidence: 99%

Autophagy Protects against Eosinophil Cytolysis and Release of DNA

Esnault

Fichtinger

Barretto

et al. 2022

Cells

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“…EMT is a complex biological process, and the regulatory network consists of multiple miRNAs and target genes, and its role in predicting GC patients has received increasing attention [15]. Many studies have reported that the EMT process is related to the lymph node metastasis process of malignant tumors [16]. Many EMT-related studies usually focus on the study of a single gene, so the conclusions drawn are often inconsistent [17,18].…”

Section: Discussionmentioning

confidence: 99%

Construction of epithelial-mesenchymal transition related miRNAs signatures as prognostic biomarkers in gastric cancer patients

Xiao

Zhang

Liu

et al. 2022

Preprint

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Aim: To identify the potential post-healing EMT related miRNAs associated with lymph node metastatic gastric cancer (LNMGC). Methods: Both RNA expression and clinical medical data were obtained from the TCGA dataset. We performed differential expression and normalization analysis of miRNAs. Cox linear regression model confirmed the differentially expressed miRNAs (DEmiRNAs) and clinical medical parameters related to overall survival (OS). The role of target genes of DEmiRNAs was determined according to the role enrichment analysis. Results: We obtained a total of 7531 DEmRNAs and 267 DEmRNAs, of which 185 DEmRNAs were down-regulated and 82 DEmRNAs were up-regulated. We randomly divided the LMNGC cases (n=291) into a training group (n=207) and a test group (n=84). The results showed that a total of 103, 11, 13 and 83 overlapping genes were associated with hsa-mir-141-3p, hsa-mir-4664-3p, hsa-mir-125b-5p and hsa-mir-7-5p, respectively. Kaplan-Meier determined that these four miRNAs can effectively distinguish high-risk and low-risk groups, and have a good indicator role (all p<0.05). Multivariate cox regression analysis also showed that EMT-related miRNA predictive model and lymph node metastasis were both prognostic risk factors (all p<0.05). The ROC curve showed that this feature had high accuracy (AUC>0.7, p<0.05). In addition, KEGG analysis showed that EMT-related pathways were mainly enriched in HIF-1 signaling pathway and focal adhesion. Conclusions: Our study demonstrated that EMT-related miRNAs could serve as independent prognostic markers in pN 1-3 GC patients.

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“…In cancer-associated autophagy, the tumor cells intentionally destroy some of their organelles to reduce their energy needs. This way, tumor cells can remain dormant until they find favorable conditions to proliferate again [ 34 ]. The interplay between EMT and autophagy is complex: autophagy may initiate or suppress EMT but is also activated by EMT-related signaling pathways, i.e., hypoxia or TGF-b [ 34 ].…”

Section: Epithelial-to-mesenchymal Transition (Emt)mentioning

confidence: 99%

“…This way, tumor cells can remain dormant until they find favorable conditions to proliferate again [ 34 ]. The interplay between EMT and autophagy is complex: autophagy may initiate or suppress EMT but is also activated by EMT-related signaling pathways, i.e., hypoxia or TGF-b [ 34 ]. One of the most important regulators of autophagy, mTOR, is also a downstream effector of the PI3K-Akt pathway of EMT [ 35 ].…”

Section: Epithelial-to-mesenchymal Transition (Emt)mentioning

confidence: 99%

Epithelial-to-Mesenchymal Transition in Metastasis: Focus on Laryngeal Carcinoma

Goulioumis

Gyftopoulos²

2022

Biomedicines

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In epithelial neoplasms, such as laryngeal carcinoma, the survival indexes deteriorate abruptly when the tumor becomes metastatic. A molecular phenomenon that normally appears during embryogenesis, epithelial-to-mesenchymal transition (EMT), is reactivated at the initial stage of metastasis when tumor cells invade the adjacent stroma. The hallmarks of this phenomenon are the abolishment of the epithelial and acquisition of mesenchymal traits by tumor cells which enhance their migratory capacity. EMT signaling is mediated by complex molecular pathways that regulate the expression of crucial molecules contributing to the tumor’s metastatic potential. Effectors of EMT include loss of adhesion, cytoskeleton remodeling, evasion of apoptosis and immune surveillance, upregulation of metalloproteinases, neovascularization, acquisition of stem-cell properties, and the activation of tumor stroma. However, the current approach to EMT involves a holistic model that incorporates the acquisition of potentials beyond mesenchymal transition. As EMT is inevitably associated with a reverse mesenchymal-to-epithelial transition (MET), a model of partial EMT is currently accepted, signifying the cell plasticity associated with invasion and metastasis. In this review, we identify the cumulative evidence which suggests that various aspects of EMT theory apply to laryngeal carcinoma, a tumor of significant morbidity and mortality, introducing novel molecular targets with prognostic and therapeutic potential.

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Autophagy and EMT in cancer and metastasis: Who controls whom?

Cited by 56 publications

References 129 publications

Autophagy Protects against Eosinophil Cytolysis and Release of DNA

Autophagy Protects against Eosinophil Cytolysis and Release of DNA

Construction of epithelial-mesenchymal transition related miRNAs signatures as prognostic biomarkers in gastric cancer patients

Epithelial-to-Mesenchymal Transition in Metastasis: Focus on Laryngeal Carcinoma

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