PMID- 33446568
OWN - NLM
STAT- MEDLINE
DCOM- 20210903
LR  - 20240102
IS  - 1549-5477 (Electronic)
IS  - 0890-9369 (Print)
IS  - 0890-9369 (Linking)
VI  - 35
IP  - 3-4
DP  - 2021 Feb 1
TI  - ATDC binds to KEAP1 to drive NRF2-mediated tumorigenesis and chemoresistance in 
      pancreatic cancer.
PG  - 218-233
LID - 10.1101/gad.344184.120 [doi]
AB  - Pancreatic ductal adenocarcinoma is a lethal disease characterized by late 
      diagnosis, propensity for early metastasis and resistance to chemotherapy. Little 
      is known about the mechanisms that drive innate therapeutic resistance in 
      pancreatic cancer. The ataxia-telangiectasia group D-associated gene (ATDC) is 
      overexpressed in pancreatic cancer and promotes tumor growth and metastasis. Our 
      study reveals that increased ATDC levels protect cancer cells from reactive 
      oxygen species (ROS) via stabilization of nuclear factor erythroid 2-related 
      factor 2 (NRF2). Mechanistically, ATDC binds to Kelch-like ECH-associated protein 
      1 (KEAP1), the principal regulator of NRF2 degradation, and thereby prevents 
      degradation of NRF2 resulting in activation of a NRF2-dependent transcriptional 
      program, reduced intracellular ROS and enhanced chemoresistance. Our findings 
      define a novel role of ATDC in regulating redox balance and chemotherapeutic 
      resistance by modulating NRF2 activity.
CI  - (c) 2021 Purohit et al.; Published by Cold Spring Harbor Laboratory Press.
FAU - Purohit, Vinee
AU  - Purohit V
AD  - Perlmutter Cancer Center, New York University, New York, New York 10016, USA.
FAU - Wang, Lidong
AU  - Wang L
AD  - Perlmutter Cancer Center, New York University, New York, New York 10016, USA.
FAU - Yang, Huibin
AU  - Yang H
AD  - Department of Radiation Oncology, University of Michigan Health System, Ann 
      Arbor, Michigan 48109, USA.
FAU - Li, Jiufeng
AU  - Li J
AD  - Perlmutter Cancer Center, New York University, New York, New York 10016, USA.
FAU - Ney, Gina M
AU  - Ney GM
AD  - Department of Pediatric Oncology, University of Michigan Health System, Ann 
      Arbor, Michigan 48109, USA.
FAU - Gumkowski, Erica R
AU  - Gumkowski ER
AD  - Department of Molecular and Integrative Physiology, University of Michigan Health 
      System, Ann Arbor, Michigan 48109, USA.
FAU - Vaidya, Akash J
AU  - Vaidya AJ
AD  - Department of Molecular and Integrative Physiology, University of Michigan Health 
      System, Ann Arbor, Michigan 48109, USA.
FAU - Wang, Annie
AU  - Wang A
AD  - Perlmutter Cancer Center, New York University, New York, New York 10016, USA.
AD  - Department of Surgery, New York University, New York, New York 10016, USA.
FAU - Bhardwaj, Amit
AU  - Bhardwaj A
AD  - Perlmutter Cancer Center, New York University, New York, New York 10016, USA.
FAU - Zhao, Ende
AU  - Zhao E
AD  - Perlmutter Cancer Center, New York University, New York, New York 10016, USA.
FAU - Dolgalev, Igor
AU  - Dolgalev I
AD  - Perlmutter Cancer Center, New York University, New York, New York 10016, USA.
FAU - Zamperone, Andrea
AU  - Zamperone A
AD  - Perlmutter Cancer Center, New York University, New York, New York 10016, USA.
FAU - Abel, Ethan V
AU  - Abel EV
AD  - Department of Molecular and Integrative Physiology, University of Michigan Health 
      System, Ann Arbor, Michigan 48109, USA.
FAU - Magliano, Marina Pasca Di
AU  - Magliano MPD
AUID- ORCID: 0000-0001-9632-9035
AD  - Department of Surgery, University of Michigan Health System, Ann Arbor, Michigan 
      48109, USA.
AD  - Department of Cell and Developmental Biology, University of Michigan Health 
      System, Ann Arbor, Michigan 48109, USA.
FAU - Crawford, Howard C
AU  - Crawford HC
AD  - Department of Molecular and Integrative Physiology, University of Michigan Health 
      System, Ann Arbor, Michigan 48109, USA.
AD  - Department of Internal Medicine, University of Michigan Health System, Ann Arbor, 
      Michigan 48109, USA.
FAU - Diolaiti, Daniel
AU  - Diolaiti D
AD  - Perlmutter Cancer Center, New York University, New York, New York 10016, USA.
FAU - Papagiannakopoulos, Thales Y
AU  - Papagiannakopoulos TY
AD  - Perlmutter Cancer Center, New York University, New York, New York 10016, USA.
AD  - Department of Pathology, New York University, New York, New York 10016, USA.
FAU - Lyssiotis, Costas A
AU  - Lyssiotis CA
AUID- ORCID: 0000-0001-9309-6141
AD  - Department of Molecular and Integrative Physiology, University of Michigan Health 
      System, Ann Arbor, Michigan 48109, USA.
AD  - Department of Internal Medicine, University of Michigan Health System, Ann Arbor, 
      Michigan 48109, USA.
FAU - Simeone, Diane M
AU  - Simeone DM
AD  - Perlmutter Cancer Center, New York University, New York, New York 10016, USA.
AD  - Department of Surgery, New York University, New York, New York 10016, USA.
AD  - Department of Pathology, New York University, New York, New York 10016, USA.
LA  - eng
GR  - R01 CA174836/CA/NCI NIH HHS/United States
GR  - R01 CA248160/CA/NCI NIH HHS/United States
GR  - R01 CA244931/CA/NCI NIH HHS/United States
GR  - R01 CA131045/CA/NCI NIH HHS/United States
GR  - R01 CA247516/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20210114
PL  - United States
TA  - Genes Dev
JT  - Genes & development
JID - 8711660
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (KEAP1 protein, human)
RN  - 0 (Kelch-Like ECH-Associated Protein 1)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (NFE2L2 protein, human)
RN  - 0 (TRIM29 protein, human)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Carcinogenesis/*genetics
MH  - DNA-Binding Proteins/*metabolism
MH  - Drug Resistance, Neoplasm/*genetics
MH  - Humans
MH  - Kelch-Like ECH-Associated Protein 1/*metabolism
MH  - NF-E2-Related Factor 2/*metabolism
MH  - Pancreatic Neoplasms/*physiopathology
MH  - Protein Binding
MH  - Transcription Factors/*metabolism
PMC - PMC7849366
OTO - NOTNLM
OT  - ATDC (Trim29)
OT  - chemotherapeutic resistance
OT  - pancreatic cancer
OT  - tumor growth and invasion
EDAT- 2021/01/16 06:00
MHDA- 2021/09/04 06:00
PMCR- 2021/08/01
CRDT- 2021/01/15 05:46
PHST- 2020/08/25 00:00 [received]
PHST- 2020/11/25 00:00 [accepted]
PHST- 2021/01/16 06:00 [pubmed]
PHST- 2021/09/04 06:00 [medline]
PHST- 2021/01/15 05:46 [entrez]
PHST- 2021/08/01 00:00 [pmc-release]
AID - gad.344184.120 [pii]
AID - 10.1101/gad.344184.120 [doi]
PST - ppublish
SO  - Genes Dev. 2021 Feb 1;35(3-4):218-233. doi: 10.1101/gad.344184.120. Epub 2021 Jan 
      14.