SPANX Control of Lamin A/C Modulates Nuclear Architecture and Promotes Melanoma Growth.


Journal

Molecular cancer research : MCR
ISSN: 1557-3125
Titre abrégé: Mol Cancer Res
Pays: United States
ID NLM: 101150042

Informations de publication

Date de publication:
10 2020
Historique:
received: 30 03 2020
revised: 19 05 2020
accepted: 15 06 2020
pubmed: 24 6 2020
medline: 1 9 2021
entrez: 24 6 2020
Statut: ppublish

Résumé

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 naïve 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.

Identifiants

pubmed: 32571981
pii: 1541-7786.MCR-20-0291
doi: 10.1158/1541-7786.MCR-20-0291
pmc: PMC7541784
mid: NIHMS1605968
doi:

Substances chimiques

Lamin Type A 0
Lamins 0
Nuclear Proteins 0
lamin C protein, human 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1560-1573

Subventions

Organisme : NCI NIH HHS
ID : R35 CA197465
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA010815
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA114046
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA030199
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA224070
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA202021
Pays : United States

Informations de copyright

©2020 American Association for Cancer Research.

Références

Oncogene. 2020 Jan;39(3):516-529
pubmed: 31541194
Oncotarget. 2016 Mar 22;7(12):14708-26
pubmed: 26895102
Front Oncol. 2018 Nov 20;8:529
pubmed: 30524960
Nat Commun. 2016 May 27;7:11752
pubmed: 27230542
Cell Rep. 2013 Sep 12;4(5):959-73
pubmed: 23994473
Cancer Res. 1999 Dec 15;59(24):6223-9
pubmed: 10626816
Oncotarget. 2016 Jul 12;7(28):44417-44429
pubmed: 27323831
Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):3077-82
pubmed: 14973187
J Struct Biol. 2000 Apr;129(2-3):324-34
pubmed: 10806083
Aging Cell. 2007 Apr;6(2):139-53
pubmed: 17274801
PLoS One. 2014 Sep 17;9(9):e107905
pubmed: 25229454
J Cell Biol. 1990 Sep;111(3):1047-57
pubmed: 2202732
Adv Exp Med Biol. 2014;773:127-42
pubmed: 24563346
Biochem Biophys Res Commun. 2019 Sep 17;517(2):188-192
pubmed: 31327494
Nat Cell Biol. 2015 Aug;17(8):1049-61
pubmed: 26147250
EMBO Rep. 2012 Dec;13(12):1070-8
pubmed: 23146893
J Cell Biol. 2008 Apr 21;181(2):269-80
pubmed: 18426975
Sci Rep. 2020 Feb 6;10(1):1971
pubmed: 32029850
Cold Spring Harb Perspect Biol. 2010 Nov;2(11):a000547
pubmed: 20826548
Cell. 2013 Jul 3;154(1):47-60
pubmed: 23827674
Annu Rev Biomed Eng. 2014 Jul 11;16:321-46
pubmed: 25014786
J Cell Sci. 2015 Aug 1;128(15):2830-41
pubmed: 26092935
Exp Dermatol. 2015 May;24(5):377-80
pubmed: 25739758
Cancer Treat Res. 2016;167:1-15
pubmed: 26601857
Blood. 2003 Feb 1;101(3):955-60
pubmed: 12393489
Nature. 2018 Jan 25;553(7689):467-472
pubmed: 29342134
Clin Cancer Res. 2009 Mar 15;15(6):1954-63
pubmed: 19276289
Nature. 2005 Sep 22;437(7058):564-8
pubmed: 16079796
Nature. 2017 Aug 24;548(7668):466-470
pubmed: 28759889
Clin Cancer Res. 2016 Apr 1;22(7):1592-602
pubmed: 26673799
Cell Rep. 2013 Jun 27;3(6):1840-6
pubmed: 23770239
Stem Cells. 2015 Sep;33(9):2652-63
pubmed: 26013162
Immunity. 2006 Sep;25(3):349-60
pubmed: 16979567
N Engl J Med. 2006 Jul 6;355(1):51-65
pubmed: 16822996
Gene. 2003 May 8;309(2):125-33
pubmed: 12758128
Mol Biol Cell. 2014 May;25(9):1493-510
pubmed: 24623722
Nat Immunol. 2016 Sep 20;17(10):1142-9
pubmed: 27648547
Trends Cell Biol. 2014 Apr;24(4):247-56
pubmed: 24309562
J Invest Dermatol. 2020 Apr 29;:
pubmed: 32360601
Cell. 2019 Jul 11;178(2):302-315.e23
pubmed: 31299200
Am J Dermatopathol. 2009 Apr;31(2):182-6
pubmed: 19318807
Nucleic Acids Res. 2018 Jan 4;46(D1):D649-D655
pubmed: 29145629
Int J Mol Sci. 2017 Nov 06;18(11):
pubmed: 29113112
Cell Rep. 2018 Feb 20;22(8):2006-2015
pubmed: 29466729
Biol Reprod. 2001 Jan;64(1):345-58
pubmed: 11133693
Annu Rev Biochem. 2015;84:131-64
pubmed: 25747401
Clin Cancer Res. 2004 Jan 1;10(1 Pt 1):101-12
pubmed: 14734458
Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15623-8
pubmed: 9861020
Nature. 2017 Oct 19;550(7676):402-406
pubmed: 28976970
Nat Rev Cancer. 2009 Jun;9(6):400-14
pubmed: 19440234
Genes Dev. 2008 Apr 1;22(7):832-53
pubmed: 18381888

Auteurs

Ikrame Lazar (I)

Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California.
Technion Integrated Cancer Center, Faculty of Medicine, Technion Institute of Technology, Haifa, Israel.

Bertrand Fabre (B)

Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California.
Technion Integrated Cancer Center, Faculty of Medicine, Technion Institute of Technology, Haifa, Israel.

Yongmei Feng (Y)

Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California.

Ali Khateb (A)

Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California.
Technion Integrated Cancer Center, Faculty of Medicine, Technion Institute of Technology, Haifa, Israel.

Patrick Turko (P)

Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland.

Julia M Martinez Gomez (JM)

Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland.

Dennie T Frederick (DT)

Massachusetts General Hospital Cancer Center, Boston, Massachusetts.

Mitchell P Levesque (MP)

Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland.

Lea Feld (L)

Technion Integrated Cancer Center, Faculty of Medicine, Technion Institute of Technology, Haifa, Israel.

Gao Zhang (G)

The Wistar Institute, Philadelphia, Pennsylvania.

Tongwu Zhang (T)

Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, NCI, Bethesda, Maryland.

Brian James (B)

Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California.

Jeny Shklover (J)

Technion Integrated Cancer Center, Faculty of Medicine, Technion Institute of Technology, Haifa, Israel.

Emily Avitan-Hersh (E)

Technion Integrated Cancer Center, Faculty of Medicine, Technion Institute of Technology, Haifa, Israel.

Ido Livneh (I)

Technion Integrated Cancer Center, Faculty of Medicine, Technion Institute of Technology, Haifa, Israel.

Marzia Scortegagna (M)

Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California.

Kevin Brown (K)

Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, NCI, Bethesda, Maryland.

Ola Larsson (O)

Department of Oncology-Pathology, Science for Life Laboratory, Karolinska Institutet, Stockholm, Sweden.

Ivan Topisirovic (I)

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.

Haguy Wolfenson (H)

Technion Integrated Cancer Center, Faculty of Medicine, Technion Institute of Technology, Haifa, Israel.

Meenhard Herlyn (M)

The Wistar Institute, Philadelphia, Pennsylvania.

Keith Flaherty (K)

Massachusetts General Hospital Cancer Center, Boston, Massachusetts.

Reinhard Dummer (R)

Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland.

Ze'ev A Ronai (ZA)

Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California. ronai@sbpdiscovery.org.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH