PMID- 33879021
OWN - NLM
STAT- MEDLINE
DCOM- 20210527
LR  - 20220429
IS  - 1554-8635 (Electronic)
IS  - 1554-8627 (Print)
IS  - 1554-8627 (Linking)
VI  - 17
IP  - 5
DP  - 2021 May
TI  - Macropinocytosis: the big drinker behind cancer cell self-consumption.
PG  - 1290-1291
LID - 10.1080/15548627.2021.1919969 [doi]
AB  - Poorly vascularized tumors embedded within a thick desmoplastic stroma, like 
      pancreatic ductal adenocarcinoma (PDAC), are nutritionally stressed. Such tumors 
      are also hypoxic and rely on a number of adaptive responses, including 
      macroautophagy/autophagy and macropinocytosis (MP), to support their bioenergetic 
      needs. Whereas autophagy enables starved cells to recycle intracellular 
      macromolecules via lysosomal degradation and use the liberated amino acids (AA) 
      to fuel their metabolism, MP allows cells to take up extracellular proteins via 
      fluid-phase endocytosis and use them as an energy source. However, how any 
      MP-enabled organism, including the prototypical cancer cell, coordinately 
      regulates and balances autophagy and MP is not fully understood. We recently 
      found that inhibition of autophagy results in upregulation of MP, which enables 
      cancer cells to overcome autophagy deficiency and continue to support their 
      bioenergetic demands. The NFE2L2/NRF2-driven induction of MP-related genes (MRGs) 
      is responsible for the upregulation of MP in autophagy inhibited, hypoxic, and 
      oxidatively stressed-exposed cancer cells. Concurrent autophagy and MP blockade 
      effectively cuts off the cancer cell's nutrient and supplies, leading to rapid 
      tumor regression. These findings suggest MP to be an important target in cancer 
      treatment and that shutting off the energy spigot is a promising therapeutic 
      strategy.Abbreviations AA: amino acids; ADCs: autophagy deficient-cells; AI: 
      autophagy inhibition; ALB: albumin; CHUK/IKKalpha: component of inhibitor of nuclear 
      factor kappa B kinase complex; CQ: chloroquine; ECM: extracellular matrix; HCQ: 
      hydroxychloroquine; MI: MP inhibition; MP: macropinocytosis; MRGs: MP-related 
      genes; MRPs: MP-related proteins; PDAC: pancreatic ductal adenocarcinoma.
FAU - Su, Hua
AU  - Su H
AUID- ORCID: 0000-0003-2344-3886
AD  - Laboratory of Gene Regulation and Signal Transduction, Departments of 
      Pharmacology and Pathology, School of Medicine, University of California San 
      Diego, La Jolla, CA, USA.
AD  - Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of 
      Nanjing University Medical School, Nanjing, Jiangsu, China.
FAU - Yang, Fei
AU  - Yang F
AD  - Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of 
      Nanjing University Medical School, Nanjing, Jiangsu, China.
FAU - Sun, Beicheng
AU  - Sun B
AD  - Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of 
      Nanjing University Medical School, Nanjing, Jiangsu, China.
FAU - Karin, Michael
AU  - Karin M
AD  - Laboratory of Gene Regulation and Signal Transduction, Departments of 
      Pharmacology and Pathology, School of Medicine, University of California San 
      Diego, La Jolla, CA, USA.
LA  - eng
GR  - P01 DK098108/DK/NIDDK NIH HHS/United States
GR  - R01 CA211794/CA/NCI NIH HHS/United States
GR  - R37 AI043477/AI/NIAID NIH HHS/United States
PT  - Comment
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210427
PL  - United States
TA  - Autophagy
JT  - Autophagy
JID - 101265188
RN  - 0 (NF-E2-Related Factor 2)
SB  - IM
CON - Cancer Cell. 2021 May 10;39(5):678-693.e11. PMID: 33740421
MH  - Autophagy
MH  - *Carcinoma, Pancreatic Ductal
MH  - Humans
MH  - NF-E2-Related Factor 2
MH  - *Pancreatic Neoplasms
MH  - Pinocytosis
PMC - PMC8143249
OTO - NOTNLM
OT  - Autophagy
OT  - NRF2
OT  - PDAC
OT  - cancer
OT  - macropinocytosis
OT  - metabolism
COIS- No potential conflict of interest was reported by the author(s).
EDAT- 2021/04/22 06:00
MHDA- 2021/05/28 06:00
PMCR- 2022/04/27
CRDT- 2021/04/21 05:34
PHST- 2021/04/22 06:00 [pubmed]
PHST- 2021/05/28 06:00 [medline]
PHST- 2021/04/21 05:34 [entrez]
PHST- 2022/04/27 00:00 [pmc-release]
AID - 1919969 [pii]
AID - 10.1080/15548627.2021.1919969 [doi]
PST - ppublish
SO  - Autophagy. 2021 May;17(5):1290-1291. doi: 10.1080/15548627.2021.1919969. Epub 
      2021 Apr 27.