scholarly journals Autophagy and Its Relationship to Epithelial to Mesenchymal Transition: When Autophagy Inhibition for Cancer Therapy Turns Counterproductive

Biology ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 71 ◽  
Author(s):  
Guadalupe Rojas-Sanchez ◽  
Israel Cotzomi-Ortega ◽  
Nidia G. Pazos-Salazar ◽  
Julio Reyes-Leyva ◽  
Paola Maycotte

The manipulation of autophagy for cancer therapy has gained recent interest in clinical settings. Although inhibition of autophagy is currently being used in clinical trials for the treatment of several malignancies, autophagy has been shown to have diverse implications for normal cell homeostasis, cancer cell survival, and signaling to cells in the tumor microenvironment. Among these implications and of relevance for cancer therapy, the autophagic process is known to be involved in the regulation of protein secretion, in tumor cell immunogenicity, and in the regulation of epithelial-to-mesenchymal transition (EMT), a critical step in the process of cancer cell invasion. In this work, we have reviewed recent evidence linking autophagy to the regulation of EMT in cancer and normal epithelial cells, and have discussed important implications for the manipulation of autophagy during cancer therapy.

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Siddharth Manvati ◽  
Kailash Chandra Mangalhara ◽  
Ponnuswamy Kalaiarasan ◽  
Rupali Chopra ◽  
Gaurav Agarwal ◽  
...  

2021 ◽  
Vol 11 ◽  
Author(s):  
Tao Wang ◽  
Ping Chen ◽  
Ruochen Dong ◽  
Scott Weir ◽  
Michael Baltezor ◽  
...  

Pancreatic cancer cell epithelial-to-mesenchymal transition (EMT) is an important contributor to cell invasion and tumor progression. Therefore, targeting EMT may be beneficial for pancreatic cancer treatment. The aim of the present study was to report on the inhibitory effect of the novel compound C150 on the EMT of pancreatic cancer cells. C150 inhibited cell proliferation in multiple pancreatic cancer cells with IC50 values of 1-2.5 μM, while in an non-cancerous pancreatic epithelial cell line hTERT-HPNE the IC50 value was >12.5 μM. C150 significantly inhibited pancreatic cancer cell migration and invasion, as demonstrated by 3-dimensional cell invasion, wound healing and Boyden chamber Transwell migration-invasion assays. Moreover, C150 treatment decreased MMP-2 gene expression in PANC-1 cells and reduced MMP-2 activity in gelatin zymography assay. In an orthotopic mouse model of pancreatic cancer, C150 significantly reduced tumor growth at the dose of 15 mg/kg by intraperitoneal injection three times per week. Furthermore, C150 enhanced protein degradation of Snail, an important EMT-promoting transcription factor, and decreased the expression of the mesenchymal marker N-cadherin, while it increased the expression of the epithelial markers zonula occludens-1 and claudin-1. The findings of the present study suggested that C150 is a novel EMT inhibitor that may be promising for inhibiting pancreatic cancer growth and metastasis.


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