Calsequestrin 2 overexpression in breast cancer increases tumorigenesis and metastasis by modulating the tumor microenvironment.
Calsequestrin
/ genetics
Carcinogenesis
Cell Line, Tumor
Epithelial-Mesenchymal Transition
/ genetics
Extracellular Matrix
/ pathology
Female
Gene Expression Regulation, Neoplastic
Humans
Hypoxia-Inducible Factor 1, alpha Subunit
/ metabolism
Models, Biological
Neoplasm Metastasis
Phenotype
Signal Transduction
Triple Negative Breast Neoplasms
/ genetics
Tumor Microenvironment
breast cancer
calsequestrin 2
metastasis
tumor microenvironment
Journal
Molecular oncology
ISSN: 1878-0261
Titre abrégé: Mol Oncol
Pays: United States
ID NLM: 101308230
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
revised:
05
10
2021
received:
02
04
2021
accepted:
04
11
2021
pubmed:
8
11
2021
medline:
2
4
2022
entrez:
7
11
2021
Statut:
ppublish
Résumé
The spatial tumor shape is determined by the complex interactions between tumor cells and their microenvironment. Here, we investigated the role of a newly identified breast cancer-related gene, calsequestrin 2 (CASQ2), in tumor-microenvironment interactions during tumor growth and metastasis. We analyzed gene expression and three-dimensional tumor shape data from the breast cancer dataset of The Cancer Genome Atlas (TCGA) and identified CASQ2 as a potential regulator of tumor-microenvironment interaction. In TCGA breast cancer cases containing information of three-dimensional tumor shapes, CASQ2 mRNA showed the highest correlation with the spatial tumor shapes. Furthermore, we investigated the expression pattern of CASQ2 in human breast cancer tissues. CASQ2 was not detected in breast cancer cell lines in vitro but was induced in the xenograft tumors and human breast cancer tissues. To evaluate the role of CASQ2, we established CASQ2-overexpressing breast cancer cell lines for in vitro and in vivo experiments. CASQ2 overexpression in breast cancer cells resulted in a more aggressive phenotype and altered epithelial-mesenchymal transition (EMT) markers in vitro. CASQ2 overexpression induced cancer-associated fibroblast characteristics along with increased hypoxia-inducible factor 1α (HIF1α) expression in stromal fibroblasts. CASQ2 overexpression accelerated tumorigenesis, induced collagen structure remodeling, and increased distant metastasis in vivo. CASQ2 conferred more metaplastic features to triple-negative breast cancer cells. Our data suggest that CASQ2 is a key regulator of breast cancer tumorigenesis and metastasis by modulating diverse aspects of tumor-microenvironment interactions.
Identifiants
pubmed: 34743414
doi: 10.1002/1878-0261.13136
pmc: PMC8763655
doi:
Substances chimiques
CASQ2 protein, human
0
Calsequestrin
0
HIF1A protein, human
0
Hypoxia-Inducible Factor 1, alpha Subunit
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
466-484Subventions
Organisme : NIEHS NIH HHS
ID : 27307C0011
Pays : United States
Organisme : NIEHS NIH HHS
ID : 27305C0011
Pays : United States
Organisme : NIEHS NIH HHS
ID : 27398C0011
Pays : United States
Informations de copyright
© 2021 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
Références
FASEB J. 2013 Jan;27(1):13-24
pubmed: 23024375
J Cancer. 2017 Feb 25;8(5):761-773
pubmed: 28382138
Cell Stem Cell. 2007 Nov;1(5):555-67
pubmed: 18371393
Breast Cancer Res Treat. 2009 Sep;117(2):273-80
pubmed: 18815879
Nat Rev Cancer. 2008 May;8(5):361-75
pubmed: 18432251
J Clin Pathol. 2013 Jun;66(6):522-8
pubmed: 23372178
J Natl Cancer Inst. 1977 Jun;58(6):1795-806
pubmed: 864756
Anticancer Res. 2017 May;37(5):2173-2183
pubmed: 28476780
Signal Transduct Target Ther. 2020 Mar 12;5(1):28
pubmed: 32296047
Bioinformatics. 2021 Aug 9;37(15):2201-2202
pubmed: 33185687
Cancer Res. 2005 Jul 1;65(13):5506-11
pubmed: 15994920
Am J Physiol Heart Circ Physiol. 2012 Mar 15;302(6):H1250-60
pubmed: 22198169
Acta Radiol. 2015 Mar;56(3):269-75
pubmed: 24558165
Oncogene. 2012 Jan 12;31(2):200-12
pubmed: 21685934
Breast Cancer. 2020 May;27(3):445-455
pubmed: 32030658
JCO Clin Cancer Inform. 2019 Feb;3:1-13
pubmed: 30715927
Cell Calcium. 2019 Jul;81:21-28
pubmed: 31163289
Trends Biotechnol. 2015 Apr;33(4):230-6
pubmed: 25708906
Nat Biotechnol. 2003 Nov;21(11):1356-60
pubmed: 14595363
Cell Adh Migr. 2014;8(3):226-35
pubmed: 24714597
PLoS One. 2015 Dec 15;10(12):e0143811
pubmed: 26669540
Proc Natl Acad Sci U S A. 2005 Jun 7;102(23):8287-92
pubmed: 15928080
Transl Oncol. 2016 Aug;9(4):313-21
pubmed: 27567954
Biores Open Access. 2012 Dec;1(6):297-305
pubmed: 23514965
Br J Pharmacol. 2014 Feb;171(4):945-60
pubmed: 24460676
Diagn Pathol. 2014 Jul 16;9:139
pubmed: 25030022
BMC Med. 2006 Dec 26;4(1):38
pubmed: 17190588
Cell Calcium. 2019 Jun;80:141-151
pubmed: 31103948
Breast Cancer Res. 2010;12(5):R68
pubmed: 20813035
Math Med Biol. 2005 Jun;22(2):163-86
pubmed: 15781426
J Clin Invest. 2007 Jul;117(7):1814-23
pubmed: 17607358
Cell Adhes Commun. 1998;6(6):503-23
pubmed: 9929743
Mol Cancer Ther. 2011 Mar;10(3):448-60
pubmed: 21224390
PLoS One. 2009 Jul 03;4(7):e6146
pubmed: 19582160
J Hematol Oncol. 2019 Aug 28;12(1):86
pubmed: 31462327
Front Oncol. 2020 Apr 08;10:486
pubmed: 32322559
Nature. 2011 Apr 7;472(7341):90-4
pubmed: 21399628
Am J Pathol. 2011 Mar;178(3):1221-32
pubmed: 21356373
Pediatr Cardiol. 2012 Aug;33(6):959-67
pubmed: 22421959
Cell Commun Signal. 2020 Apr 7;18(1):59
pubmed: 32264958
Cold Spring Harb Perspect Med. 2016 Aug 01;6(8):
pubmed: 27481837
Nature. 2013 Sep 19;501(7467):355-64
pubmed: 24048068
Semin Cancer Biol. 2014 Apr;25:3-9
pubmed: 24412106
Oncogene. 2014 May 1;33(18):2307-16
pubmed: 23686305
CA Cancer J Clin. 2018 Nov;68(6):394-424
pubmed: 30207593
N Engl J Med. 2007 Jan 18;356(3):217-26
pubmed: 17229949
Mod Pathol. 2012 Feb;25(2):178-84
pubmed: 22080057
Sci Rep. 2019 Apr 19;9(1):6314
pubmed: 31004097
J Gen Physiol. 2013 Aug;142(2):127-36
pubmed: 23858002
Biomed Eng Online. 2016 Apr 27;15:46
pubmed: 27121383
Nat Commun. 2020 Apr 7;11(1):1723
pubmed: 32265444
J Biol Chem. 2009 Nov 27;284(48):33662-70
pubmed: 19801662
Nature. 2012 Apr 18;486(7403):346-52
pubmed: 22522925
Nat Rev Cancer. 2011 Jul 22;11(8):609-18
pubmed: 21779011