PMID- 32571981
OWN - NLM
STAT- MEDLINE
DCOM- 20210831
LR  - 20240214
IS  - 1557-3125 (Electronic)
IS  - 1541-7786 (Print)
IS  - 1541-7786 (Linking)
VI  - 18
IP  - 10
DP  - 2020 Oct
TI  - SPANX Control of Lamin A/C Modulates Nuclear Architecture and Promotes Melanoma 
      Growth.
PG  - 1560-1573
LID - 10.1158/1541-7786.MCR-20-0291 [doi]
AB  - Mechanisms regulating nuclear organization control fundamental cellular 
      processes, including the cell and chromatin organization. Their disorganization, 
      including aberrant nuclear architecture, has been often implicated in cellular 
      transformation. Here, we identify Lamin A, among proteins essential for nuclear 
      architecture, as SPANX (sperm protein associated with the nucleus on the X 
      chromosome), a cancer testis antigen previously linked to invasive tumor 
      phenotypes, interacting protein in melanoma. SPANX interaction with Lamin A was 
      mapped to the immunoglobulin fold-like domain, a region critical for Lamin A 
      function, which is often mutated in laminopathies. SPANX downregulation in 
      melanoma cell lines perturbed nuclear organization, decreased cell viability, and 
      promoted senescence-associated phenotypes. Moreover, SPANX knockdown (KD) in 
      melanoma cells promoted proliferation arrest, a phenotype mediated in part by 
      IRF3/IL1A signaling. SPANX KD in melanoma cells also prompted the secretion of 
      IL1A, which attenuated the proliferation of naive melanoma cells. Identification 
      of SPANX as a nuclear architecture complex component provides an unexpected 
      insight into the regulation of Lamin A and its importance in melanoma. 
      IMPLICATIONS: SPANX, a testis protein, interacts with LMNA and controls nuclear 
      architecture and melanoma growth.
CI  - (c)2020 American Association for Cancer Research.
FAU - Lazar, Ikrame
AU  - Lazar I
AD  - Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California.
AD  - Technion Integrated Cancer Center, Faculty of Medicine, Technion Institute of 
      Technology, Haifa, Israel.
FAU - Fabre, Bertrand
AU  - Fabre B
AD  - Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California.
AD  - Technion Integrated Cancer Center, Faculty of Medicine, Technion Institute of 
      Technology, Haifa, Israel.
FAU - Feng, Yongmei
AU  - Feng Y
AD  - Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California.
FAU - Khateb, Ali
AU  - Khateb A
AD  - Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California.
AD  - Technion Integrated Cancer Center, Faculty of Medicine, Technion Institute of 
      Technology, Haifa, Israel.
FAU - Turko, Patrick
AU  - Turko P
AUID- ORCID: 0000-0003-3695-8264
AD  - Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland.
FAU - Martinez Gomez, Julia M
AU  - Martinez Gomez JM
AD  - Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland.
FAU - Frederick, Dennie T
AU  - Frederick DT
AD  - Massachusetts General Hospital Cancer Center, Boston, Massachusetts.
FAU - Levesque, Mitchell P
AU  - Levesque MP
AD  - Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland.
FAU - Feld, Lea
AU  - Feld L
AD  - Technion Integrated Cancer Center, Faculty of Medicine, Technion Institute of 
      Technology, Haifa, Israel.
FAU - Zhang, Gao
AU  - Zhang G
AUID- ORCID: 0000-0001-8617-8886
AD  - The Wistar Institute, Philadelphia, Pennsylvania.
FAU - Zhang, Tongwu
AU  - Zhang T
AUID- ORCID: 0000-0003-2124-2706
AD  - Laboratory of Translational Genomics, Division of Cancer Epidemiology and 
      Genetics, NCI, Bethesda, Maryland.
FAU - James, Brian
AU  - James B
AD  - Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California.
FAU - Shklover, Jeny
AU  - Shklover J
AD  - Technion Integrated Cancer Center, Faculty of Medicine, Technion Institute of 
      Technology, Haifa, Israel.
FAU - Avitan-Hersh, Emily
AU  - Avitan-Hersh E
AUID- ORCID: 0000-0002-2154-7609
AD  - Technion Integrated Cancer Center, Faculty of Medicine, Technion Institute of 
      Technology, Haifa, Israel.
FAU - Livneh, Ido
AU  - Livneh I
AD  - Technion Integrated Cancer Center, Faculty of Medicine, Technion Institute of 
      Technology, Haifa, Israel.
FAU - Scortegagna, Marzia
AU  - Scortegagna M
AD  - Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California.
FAU - Brown, Kevin
AU  - Brown K
AD  - Laboratory of Translational Genomics, Division of Cancer Epidemiology and 
      Genetics, NCI, Bethesda, Maryland.
FAU - Larsson, Ola
AU  - Larsson O
AD  - Department of Oncology-Pathology, Science for Life Laboratory, Karolinska 
      Institutet, Stockholm, Sweden.
FAU - Topisirovic, Ivan
AU  - Topisirovic I
AUID- ORCID: 0000-0002-5510-9762
AD  - Lady Davis Institute, Sir Mortimer B. Davis Jewish General Hospital, Gerald 
      Bronfman Department of Oncology, Departments of Experimental Medicine and 
      Biochemistry, McGill University, Montreal, Quebec, Canada.
FAU - Wolfenson, Haguy
AU  - Wolfenson H
AUID- ORCID: 0000-0001-6892-7839
AD  - Technion Integrated Cancer Center, Faculty of Medicine, Technion Institute of 
      Technology, Haifa, Israel.
FAU - Herlyn, Meenhard
AU  - Herlyn M
AD  - The Wistar Institute, Philadelphia, Pennsylvania.
FAU - Flaherty, Keith
AU  - Flaherty K
AD  - Massachusetts General Hospital Cancer Center, Boston, Massachusetts.
FAU - Dummer, Reinhard
AU  - Dummer R
AD  - Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland.
FAU - Ronai, Ze'ev A
AU  - Ronai ZA
AD  - Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California. 
      ronai@sbpdiscovery.org.
LA  - eng
GR  - R35 CA197465/CA/NCI NIH HHS/United States
GR  - P30 CA010815/CA/NCI NIH HHS/United States
GR  - P01 CA114046/CA/NCI NIH HHS/United States
GR  - P30 CA030199/CA/NCI NIH HHS/United States
GR  - P50 CA174523/CA/NCI NIH HHS/United States
GR  - U54 CA224070/CA/NCI NIH HHS/United States
GR  - R01 CA202021/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20200622
PL  - United States
TA  - Mol Cancer Res
JT  - Molecular cancer research : MCR
JID - 101150042
RN  - 0 (Lamin Type A)
RN  - 0 (Lamins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (lamin C protein, human)
SB  - IM
MH  - Humans
MH  - Lamin Type A/*metabolism
MH  - Lamins/*metabolism
MH  - Melanoma/*genetics/pathology
MH  - Nuclear Proteins/*genetics
MH  - Transfection
PMC - PMC7541784
MID - NIHMS1605968
COIS- Competing Interests: ZR is a co-founder and serves as scientific advisor to 
      Pangea Therapeutics. All other authors declare no competing interests.
EDAT- 2020/06/24 06:00
MHDA- 2021/09/01 06:00
PMCR- 2021/04/01
CRDT- 2020/06/24 06:00
PHST- 2020/03/30 00:00 [received]
PHST- 2020/05/19 00:00 [revised]
PHST- 2020/06/15 00:00 [accepted]
PHST- 2020/06/24 06:00 [pubmed]
PHST- 2021/09/01 06:00 [medline]
PHST- 2020/06/24 06:00 [entrez]
PHST- 2021/04/01 00:00 [pmc-release]
AID - 1541-7786.MCR-20-0291 [pii]
AID - 10.1158/1541-7786.MCR-20-0291 [doi]
PST - ppublish
SO  - Mol Cancer Res. 2020 Oct;18(10):1560-1573. doi: 10.1158/1541-7786.MCR-20-0291. 
      Epub 2020 Jun 22.