Proteomic and transcriptomic profiling identifies mediators of anchorage-independent growth and roles of inhibitor of differentiation proteins in invasive lobular carcinoma

Abstract Invasive lobular carcinoma (ILC) is a histological subtype of breast cancer with distinct molecular and clinical features from the more common subtype invasive ductal carcinoma (IDC). ILC cells exhibit anchorage-independent growth in ultra-low attachment (ULA) suspension cultures, which is...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Nilgun Tasdemir, Kai Ding, Laura Savariau, Kevin M. Levine, Tian Du, Ashuvinee Elangovan, Emily A. Bossart, Adrian V. Lee, Nancy E. Davidson, Steffi Oesterreich
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5857eb9ce5a941f2abcd4c9ba3a29fd8
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:5857eb9ce5a941f2abcd4c9ba3a29fd8
record_format	dspace
spelling	oai:doaj.org-article:5857eb9ce5a941f2abcd4c9ba3a29fd82021-12-02T15:33:10ZProteomic and transcriptomic profiling identifies mediators of anchorage-independent growth and roles of inhibitor of differentiation proteins in invasive lobular carcinoma10.1038/s41598-020-68141-92045-2322https://doaj.org/article/5857eb9ce5a941f2abcd4c9ba3a29fd82020-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-68141-9https://doaj.org/toc/2045-2322Abstract Invasive lobular carcinoma (ILC) is a histological subtype of breast cancer with distinct molecular and clinical features from the more common subtype invasive ductal carcinoma (IDC). ILC cells exhibit anchorage-independent growth in ultra-low attachment (ULA) suspension cultures, which is largely attributed to the loss of E-cadherin. In addition to anoikis resistance, herein we show that human ILC cell lines exhibit enhanced cell proliferation in ULA cultures as compared to IDC cells. Proteomic comparison of ILC and IDC cell lines identified induction of PI3K/Akt and p90-RSK pathways specifically in ULA culture in ILC cells. Further transcriptional profiling uncovered unique upregulation of the inhibitors of differentiation family transcription factors ID1 and ID3 in ILC ULA culture, the knockdown of which diminished the anchorage-independent growth of ILC cell lines through cell cycle arrest. We find that ID1 and ID3 expression is higher in human ILC tumors as compared to IDC, correlated with worse prognosis uniquely in patients with ILC and associated with upregulation of angiogenesis and matrisome-related genes. Altogether, our comprehensive study of anchorage independence in human ILC cell lines provides mechanistic insights and clinical implications for metastatic dissemination of ILC and implicates ID1 and ID3 as novel drivers and therapeutic targets for lobular breast cancer.Nilgun TasdemirKai DingLaura SavariauKevin M. LevineTian DuAshuvinee ElangovanEmily A. BossartAdrian V. LeeNancy E. DavidsonSteffi OesterreichNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-15 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nilgun Tasdemir Kai Ding Laura Savariau Kevin M. Levine Tian Du Ashuvinee Elangovan Emily A. Bossart Adrian V. Lee Nancy E. Davidson Steffi Oesterreich Proteomic and transcriptomic profiling identifies mediators of anchorage-independent growth and roles of inhibitor of differentiation proteins in invasive lobular carcinoma
description	Abstract Invasive lobular carcinoma (ILC) is a histological subtype of breast cancer with distinct molecular and clinical features from the more common subtype invasive ductal carcinoma (IDC). ILC cells exhibit anchorage-independent growth in ultra-low attachment (ULA) suspension cultures, which is largely attributed to the loss of E-cadherin. In addition to anoikis resistance, herein we show that human ILC cell lines exhibit enhanced cell proliferation in ULA cultures as compared to IDC cells. Proteomic comparison of ILC and IDC cell lines identified induction of PI3K/Akt and p90-RSK pathways specifically in ULA culture in ILC cells. Further transcriptional profiling uncovered unique upregulation of the inhibitors of differentiation family transcription factors ID1 and ID3 in ILC ULA culture, the knockdown of which diminished the anchorage-independent growth of ILC cell lines through cell cycle arrest. We find that ID1 and ID3 expression is higher in human ILC tumors as compared to IDC, correlated with worse prognosis uniquely in patients with ILC and associated with upregulation of angiogenesis and matrisome-related genes. Altogether, our comprehensive study of anchorage independence in human ILC cell lines provides mechanistic insights and clinical implications for metastatic dissemination of ILC and implicates ID1 and ID3 as novel drivers and therapeutic targets for lobular breast cancer.
format	article
author	Nilgun Tasdemir Kai Ding Laura Savariau Kevin M. Levine Tian Du Ashuvinee Elangovan Emily A. Bossart Adrian V. Lee Nancy E. Davidson Steffi Oesterreich
author_facet	Nilgun Tasdemir Kai Ding Laura Savariau Kevin M. Levine Tian Du Ashuvinee Elangovan Emily A. Bossart Adrian V. Lee Nancy E. Davidson Steffi Oesterreich
author_sort	Nilgun Tasdemir
title	Proteomic and transcriptomic profiling identifies mediators of anchorage-independent growth and roles of inhibitor of differentiation proteins in invasive lobular carcinoma
title_short	Proteomic and transcriptomic profiling identifies mediators of anchorage-independent growth and roles of inhibitor of differentiation proteins in invasive lobular carcinoma
title_full	Proteomic and transcriptomic profiling identifies mediators of anchorage-independent growth and roles of inhibitor of differentiation proteins in invasive lobular carcinoma
title_fullStr	Proteomic and transcriptomic profiling identifies mediators of anchorage-independent growth and roles of inhibitor of differentiation proteins in invasive lobular carcinoma
title_full_unstemmed	Proteomic and transcriptomic profiling identifies mediators of anchorage-independent growth and roles of inhibitor of differentiation proteins in invasive lobular carcinoma
title_sort	proteomic and transcriptomic profiling identifies mediators of anchorage-independent growth and roles of inhibitor of differentiation proteins in invasive lobular carcinoma
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/5857eb9ce5a941f2abcd4c9ba3a29fd8
work_keys_str_mv	AT nilguntasdemir proteomicandtranscriptomicprofilingidentifiesmediatorsofanchorageindependentgrowthandrolesofinhibitorofdifferentiationproteinsininvasivelobularcarcinoma AT kaiding proteomicandtranscriptomicprofilingidentifiesmediatorsofanchorageindependentgrowthandrolesofinhibitorofdifferentiationproteinsininvasivelobularcarcinoma AT laurasavariau proteomicandtranscriptomicprofilingidentifiesmediatorsofanchorageindependentgrowthandrolesofinhibitorofdifferentiationproteinsininvasivelobularcarcinoma AT kevinmlevine proteomicandtranscriptomicprofilingidentifiesmediatorsofanchorageindependentgrowthandrolesofinhibitorofdifferentiationproteinsininvasivelobularcarcinoma AT tiandu proteomicandtranscriptomicprofilingidentifiesmediatorsofanchorageindependentgrowthandrolesofinhibitorofdifferentiationproteinsininvasivelobularcarcinoma AT ashuvineeelangovan proteomicandtranscriptomicprofilingidentifiesmediatorsofanchorageindependentgrowthandrolesofinhibitorofdifferentiationproteinsininvasivelobularcarcinoma AT emilyabossart proteomicandtranscriptomicprofilingidentifiesmediatorsofanchorageindependentgrowthandrolesofinhibitorofdifferentiationproteinsininvasivelobularcarcinoma AT adrianvlee proteomicandtranscriptomicprofilingidentifiesmediatorsofanchorageindependentgrowthandrolesofinhibitorofdifferentiationproteinsininvasivelobularcarcinoma AT nancyedavidson proteomicandtranscriptomicprofilingidentifiesmediatorsofanchorageindependentgrowthandrolesofinhibitorofdifferentiationproteinsininvasivelobularcarcinoma AT steffioesterreich proteomicandtranscriptomicprofilingidentifiesmediatorsofanchorageindependentgrowthandrolesofinhibitorofdifferentiationproteinsininvasivelobularcarcinoma
_version_	1718387082583343104

Proteomic and transcriptomic profiling identifies mediators of anchorage-independent growth and roles of inhibitor of differentiation proteins in invasive lobular carcinoma

Ejemplares similares