Mitophagy in Pancreatic Cancer
Pancreatic ductal adenocarcinoma (PDAC), one of the most aggressive solid malignancies, is characterized by the presence of oncogenic KRAS mutations, poor response to current therapies, prone to metastasis, and a low 5-year overall survival rate. Macroautophagy (herein referred to as autophagy) is a...
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doaj-f2bdf70dc8b04f76ab36c814e358e36f2021-02-26T15:05:50ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-02-011110.3389/fonc.2021.616079616079Mitophagy in Pancreatic CancerYangchun Xie0Jiao Liu1Rui Kang2Daolin Tang3Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha, ChinaThe Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, ChinaDepartment of Surgery, UT Southwestern Medical Center, Dallas, TX, United StatesDepartment of Surgery, UT Southwestern Medical Center, Dallas, TX, United StatesPancreatic ductal adenocarcinoma (PDAC), one of the most aggressive solid malignancies, is characterized by the presence of oncogenic KRAS mutations, poor response to current therapies, prone to metastasis, and a low 5-year overall survival rate. Macroautophagy (herein referred to as autophagy) is a lysosome-dependent degradation system that forms a series of dynamic membrane structures to engulf, degrade, and recycle various cargoes, such as unused proteins, damaged organelles, and invading pathogens. Autophagy is usually upregulated in established cancers, but it plays a dual role in the regulation of the initiation and progression of PDAC. As a type of selective autophagy, mitophagy is a mitochondrial quality control mechanism that uses ubiquitin-dependent (e.g., the PINK1-PRKN pathway) and -independent (e.g., BNIP3L/NIX, FUNDC1, and BNIP3) pathways to regulate mitochondrial turnover and participate in the modulation of metabolism and cell death. Genetically engineered mouse models indicate that the loss of PINK1 or PRKN promotes, whereas the depletion of BNIP3L inhibits oncogenic KRAS-driven pancreatic tumorigenesis. Mitophagy also play a dual role in the regulation of the anticancer activity of certain cytotoxic agents (e.g., rocaglamide A, dichloroacetate, fisetin, and P. suffruticosa extracts) in PDAC cells or xenograft models. In this min-review, we summarize the latest advances in understanding the complex role of mitophagy in the occurrence and treatment of PDAC.https://www.frontiersin.org/articles/10.3389/fonc.2021.616079/fullmitophagyautophagyPDAC - pancreatic ductal adenocarcinomatumorigenesistherapy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yangchun Xie Jiao Liu Rui Kang Daolin Tang |
spellingShingle |
Yangchun Xie Jiao Liu Rui Kang Daolin Tang Mitophagy in Pancreatic Cancer Frontiers in Oncology mitophagy autophagy PDAC - pancreatic ductal adenocarcinoma tumorigenesis therapy |
author_facet |
Yangchun Xie Jiao Liu Rui Kang Daolin Tang |
author_sort |
Yangchun Xie |
title |
Mitophagy in Pancreatic Cancer |
title_short |
Mitophagy in Pancreatic Cancer |
title_full |
Mitophagy in Pancreatic Cancer |
title_fullStr |
Mitophagy in Pancreatic Cancer |
title_full_unstemmed |
Mitophagy in Pancreatic Cancer |
title_sort |
mitophagy in pancreatic cancer |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Oncology |
issn |
2234-943X |
publishDate |
2021-02-01 |
description |
Pancreatic ductal adenocarcinoma (PDAC), one of the most aggressive solid malignancies, is characterized by the presence of oncogenic KRAS mutations, poor response to current therapies, prone to metastasis, and a low 5-year overall survival rate. Macroautophagy (herein referred to as autophagy) is a lysosome-dependent degradation system that forms a series of dynamic membrane structures to engulf, degrade, and recycle various cargoes, such as unused proteins, damaged organelles, and invading pathogens. Autophagy is usually upregulated in established cancers, but it plays a dual role in the regulation of the initiation and progression of PDAC. As a type of selective autophagy, mitophagy is a mitochondrial quality control mechanism that uses ubiquitin-dependent (e.g., the PINK1-PRKN pathway) and -independent (e.g., BNIP3L/NIX, FUNDC1, and BNIP3) pathways to regulate mitochondrial turnover and participate in the modulation of metabolism and cell death. Genetically engineered mouse models indicate that the loss of PINK1 or PRKN promotes, whereas the depletion of BNIP3L inhibits oncogenic KRAS-driven pancreatic tumorigenesis. Mitophagy also play a dual role in the regulation of the anticancer activity of certain cytotoxic agents (e.g., rocaglamide A, dichloroacetate, fisetin, and P. suffruticosa extracts) in PDAC cells or xenograft models. In this min-review, we summarize the latest advances in understanding the complex role of mitophagy in the occurrence and treatment of PDAC. |
topic |
mitophagy autophagy PDAC - pancreatic ductal adenocarcinoma tumorigenesis therapy |
url |
https://www.frontiersin.org/articles/10.3389/fonc.2021.616079/full |
work_keys_str_mv |
AT yangchunxie mitophagyinpancreaticcancer AT jiaoliu mitophagyinpancreaticcancer AT ruikang mitophagyinpancreaticcancer AT daolintang mitophagyinpancreaticcancer |
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