PMID- 30982660
OWN - NLM
STAT- MEDLINE
DCOM- 20200106
LR  - 20200507
IS  - 1878-1551 (Electronic)
IS  - 1534-5807 (Print)
IS  - 1534-5807 (Linking)
VI  - 49
IP  - 3
DP  - 2019 May 6
TI  - Loss of Sirtuin 1 Alters the Secretome of Breast Cancer Cells by Impairing 
      Lysosomal Integrity.
PG  - 393-408.e7
LID - S1534-5807(19)30188-1 [pii]
LID - 10.1016/j.devcel.2019.03.011 [doi]
AB  - The NAD(+)-dependent deacetylase Sirtuin 1 (SIRT1) is down-regulated in 
      triple-negative breast cancer. To determine the mechanistic basis by which 
      reduced SIRT1 expression influences processes related to certain aggressive 
      cancers, we examined the consequences of depleting breast cancer cells of SIRT1. 
      We discovered that reducing SIRT1 levels decreased the expression of one 
      particular subunit of the vacuolar-type H+ ATPase (V-ATPase), which is 
      responsible for proper lysosomal acidification and protein degradation. This 
      impairment in lysosomal function caused a reduction in the number of 
      multi-vesicular bodies (MVBs) targeted for lysosomal degradation and resulted in 
      larger MVBs prior to their fusing with the plasma membrane to release their 
      contents. Collectively, these findings help explain how reduced SIRT1 expression, 
      by disrupting lysosomal function and generating a secretome comprising exosomes 
      with unique cargo and soluble hydrolases that degrade the extracellular matrix, 
      can promote processes that increase breast-cancer-cell survival and invasion.
CI  - Copyright (c) 2019 Elsevier Inc. All rights reserved.
FAU - Latifkar, Arash
AU  - Latifkar A
AD  - Department of Molecular Medicine, Cornell University, Ithaca, NY 14853, USA; 
      Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 
      14853, USA.
FAU - Ling, Lu
AU  - Ling L
AD  - Nancy E. and Peter C. Meinig School of Biomedical Engineering, Ithaca, NY 14853, 
      USA; Kavli Institute at Cornell for Nanoscale Science Cornell University, Ithaca, 
      NY 14853, USA.
FAU - Hingorani, Amrit
AU  - Hingorani A
AD  - Department of Molecular Medicine, Cornell University, Ithaca, NY 14853, USA.
FAU - Johansen, Eric
AU  - Johansen E
AD  - Department of Molecular Medicine, Cornell University, Ithaca, NY 14853, USA.
FAU - Clement, Amdiel
AU  - Clement A
AD  - Department of Molecular Medicine, Cornell University, Ithaca, NY 14853, USA.
FAU - Zhang, Xiaoyu
AU  - Zhang X
AD  - Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 
      14853, USA.
FAU - Hartman, John
AU  - Hartman J
AD  - Sibley School of Mechanical and Aerospace Engineering, Cornell University, 
      Ithaca, NY 14853, USA.
FAU - Fischbach, Claudia
AU  - Fischbach C
AD  - Nancy E. and Peter C. Meinig School of Biomedical Engineering, Ithaca, NY 14853, 
      USA; Kavli Institute at Cornell for Nanoscale Science Cornell University, Ithaca, 
      NY 14853, USA.
FAU - Lin, Hening
AU  - Lin H
AD  - Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 
      14853, USA; Howard Hughes Medical Institute, Cornell University, Ithaca, NY 
      14853, USA.
FAU - Cerione, Richard A
AU  - Cerione RA
AD  - Department of Molecular Medicine, Cornell University, Ithaca, NY 14853, USA; 
      Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 
      14853, USA. Electronic address: rac1@cornell.edu.
FAU - Antonyak, Marc A
AU  - Antonyak MA
AD  - Department of Molecular Medicine, Cornell University, Ithaca, NY 14853, USA.
LA  - eng
GR  - P30 GM124166/GM/NIGMS NIH HHS/United States
GR  - R01 CA201402/CA/NCI NIH HHS/United States
GR  - U54 CA210184/CA/NCI NIH HHS/United States
GR  - F99 CA234921/CA/NCI NIH HHS/United States
GR  - R35 GM122575/GM/NIGMS 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 - 20190411
PL  - United States
TA  - Dev Cell
JT  - Developmental cell
JID - 101120028
RN  - EC 3.5.1.- (SIRT1 protein, human)
RN  - EC 3.5.1.- (Sirtuin 1)
RN  - EC 3.6.1.- (Vacuolar Proton-Translocating ATPases)
SB  - IM
CIN - Dev Cell. 2019 May 6;49(3):302-303. PMID: 31063745
MH  - Breast Neoplasms/*metabolism/pathology
MH  - Cell Line, Tumor
MH  - Cell Survival/physiology
MH  - Exosomes/metabolism
MH  - Female
MH  - Homeostasis
MH  - Humans
MH  - Lysosomes/*metabolism
MH  - Multivesicular Bodies/metabolism
MH  - Neoplasm Invasiveness
MH  - Sirtuin 1/*deficiency/metabolism
MH  - Vacuolar Proton-Translocating ATPases/metabolism
PMC - PMC6519475
MID - NIHMS1526175
OTO - NOTNLM
OT  - cancer
OT  - cathepsin
OT  - deacetylation
OT  - exosomes
OT  - extracellular vesicles
OT  - lysosome
OT  - multi-vesicular body
OT  - secretome
OT  - sirtuin
OT  - vacuolar-type H(+) ATPase
COIS- DECLARATION OF INTEREST The authors declare no competing interests.
EDAT- 2019/04/16 06:00
MHDA- 2020/01/07 06:00
PMCR- 2020/05/06
CRDT- 2019/04/16 06:00
PHST- 2017/12/13 00:00 [received]
PHST- 2019/01/09 00:00 [revised]
PHST- 2019/03/13 00:00 [accepted]
PHST- 2019/04/16 06:00 [pubmed]
PHST- 2020/01/07 06:00 [medline]
PHST- 2019/04/16 06:00 [entrez]
PHST- 2020/05/06 00:00 [pmc-release]
AID - S1534-5807(19)30188-1 [pii]
AID - 10.1016/j.devcel.2019.03.011 [doi]
PST - ppublish
SO  - Dev Cell. 2019 May 6;49(3):393-408.e7. doi: 10.1016/j.devcel.2019.03.011. Epub 
      2019 Apr 11.