Periostin gene expression in neu-positive breast cancer cells is regulated by a FGFR signaling cross talk with TGFβ/PI3K/AKT pathways

Abstract Background Breast cancer is a highly heterogeneous disease with multiple drivers and complex regulatory networks. Periostin (Postn) is a matricellular protein involved in a plethora of cancer types and other diseases. Postn has been shown to be involved in various processes of tumor develop...

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Autores principales:	Cédrik Labrèche, David P. Cook, John Abou-Hamad, Julia Pascoal, Benjamin R. Pryce, Khalid N. Al-Zahrani, Luc A. Sabourin
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Periostin Gene regulation Breast cancer FGF AKT Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/9c9e5ccf6503486ea9f67bb494f2c5be
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spelling	oai:doaj.org-article:9c9e5ccf6503486ea9f67bb494f2c5be2021-11-28T12:09:54ZPeriostin gene expression in neu-positive breast cancer cells is regulated by a FGFR signaling cross talk with TGFβ/PI3K/AKT pathways10.1186/s13058-021-01487-81465-542Xhttps://doaj.org/article/9c9e5ccf6503486ea9f67bb494f2c5be2021-11-01T00:00:00Zhttps://doi.org/10.1186/s13058-021-01487-8https://doaj.org/toc/1465-542XAbstract Background Breast cancer is a highly heterogeneous disease with multiple drivers and complex regulatory networks. Periostin (Postn) is a matricellular protein involved in a plethora of cancer types and other diseases. Postn has been shown to be involved in various processes of tumor development, such as angiogenesis, invasion, cell survival and metastasis. The expression of Postn in breast cancer cells has been correlated with a more aggressive phenotype. Despite extensive research, it remains unclear how epithelial cancer cells regulate Postn expression. Methods Using murine tumor models and human TMAs, we have assessed the proportion of tumor samples that have acquired Postn expression in tumor cells. Using biochemical approaches and tumor cell lines derived from Neu+ murine primary tumors, we have identified major regulators of Postn gene expression in breast cancer cell lines. Results Here, we show that, while the stromal compartment typically always expresses Postn, about 50% of breast tumors acquire Postn expression in the epithelial tumor cells. Furthermore, using an in vitro model, we show a cross-regulation between FGFR, TGFβ and PI3K/AKT pathways to regulate Postn expression. In HER2-positive murine breast cancer cells, we found that basic FGF can repress Postn expression through a PKC-dependent pathway, while TGFβ can induce Postn expression in a SMAD-independent manner. Postn induction following the removal of the FGF-suppressive signal is dependent on PI3K/AKT signaling. Conclusion Overall, these results reveal a novel regulatory mechanism and shed light on how breast tumor cells acquire Postn expression. This complex regulation is likely to be cell type and cancer specific as well as have important therapeutic implications.Cédrik LabrècheDavid P. CookJohn Abou-HamadJulia PascoalBenjamin R. PryceKhalid N. Al-ZahraniLuc A. SabourinBMCarticlePeriostinGene regulationBreast cancerFGFAKTNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENBreast Cancer Research, Vol 23, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Periostin Gene regulation Breast cancer FGF AKT Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Periostin Gene regulation Breast cancer FGF AKT Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cédrik Labrèche David P. Cook John Abou-Hamad Julia Pascoal Benjamin R. Pryce Khalid N. Al-Zahrani Luc A. Sabourin Periostin gene expression in neu-positive breast cancer cells is regulated by a FGFR signaling cross talk with TGFβ/PI3K/AKT pathways
description	Abstract Background Breast cancer is a highly heterogeneous disease with multiple drivers and complex regulatory networks. Periostin (Postn) is a matricellular protein involved in a plethora of cancer types and other diseases. Postn has been shown to be involved in various processes of tumor development, such as angiogenesis, invasion, cell survival and metastasis. The expression of Postn in breast cancer cells has been correlated with a more aggressive phenotype. Despite extensive research, it remains unclear how epithelial cancer cells regulate Postn expression. Methods Using murine tumor models and human TMAs, we have assessed the proportion of tumor samples that have acquired Postn expression in tumor cells. Using biochemical approaches and tumor cell lines derived from Neu+ murine primary tumors, we have identified major regulators of Postn gene expression in breast cancer cell lines. Results Here, we show that, while the stromal compartment typically always expresses Postn, about 50% of breast tumors acquire Postn expression in the epithelial tumor cells. Furthermore, using an in vitro model, we show a cross-regulation between FGFR, TGFβ and PI3K/AKT pathways to regulate Postn expression. In HER2-positive murine breast cancer cells, we found that basic FGF can repress Postn expression through a PKC-dependent pathway, while TGFβ can induce Postn expression in a SMAD-independent manner. Postn induction following the removal of the FGF-suppressive signal is dependent on PI3K/AKT signaling. Conclusion Overall, these results reveal a novel regulatory mechanism and shed light on how breast tumor cells acquire Postn expression. This complex regulation is likely to be cell type and cancer specific as well as have important therapeutic implications.
format	article
author	Cédrik Labrèche David P. Cook John Abou-Hamad Julia Pascoal Benjamin R. Pryce Khalid N. Al-Zahrani Luc A. Sabourin
author_facet	Cédrik Labrèche David P. Cook John Abou-Hamad Julia Pascoal Benjamin R. Pryce Khalid N. Al-Zahrani Luc A. Sabourin
author_sort	Cédrik Labrèche
title	Periostin gene expression in neu-positive breast cancer cells is regulated by a FGFR signaling cross talk with TGFβ/PI3K/AKT pathways
title_short	Periostin gene expression in neu-positive breast cancer cells is regulated by a FGFR signaling cross talk with TGFβ/PI3K/AKT pathways
title_full	Periostin gene expression in neu-positive breast cancer cells is regulated by a FGFR signaling cross talk with TGFβ/PI3K/AKT pathways
title_fullStr	Periostin gene expression in neu-positive breast cancer cells is regulated by a FGFR signaling cross talk with TGFβ/PI3K/AKT pathways
title_full_unstemmed	Periostin gene expression in neu-positive breast cancer cells is regulated by a FGFR signaling cross talk with TGFβ/PI3K/AKT pathways
title_sort	periostin gene expression in neu-positive breast cancer cells is regulated by a fgfr signaling cross talk with tgfβ/pi3k/akt pathways
publisher	BMC
publishDate	2021
url	https://doaj.org/article/9c9e5ccf6503486ea9f67bb494f2c5be
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Periostin gene expression in neu-positive breast cancer cells is regulated by a FGFR signaling cross talk with TGFβ/PI3K/AKT pathways

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