Estrogen receptor variant ERα46 and insulin receptor drive in primary breast cancer cells growth effects and interleukin 11 induction prompting the motility of cancer‐associated fibroblasts

Abstract Among the prognostic and predictive biomarkers of breast cancer (BC), the role of estrogen receptor (ER)α wild‐type has been acknowledged, although the action of certain ERα splice variants has not been elucidated. Insulin/insulin receptor (IR) axis has also been involved in the progression...

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Autores principales:	Francesca Cirillo, Michele Pellegrino, Marianna Talia, Ida Daniela Perrotta, Damiano Cosimo Rigiracciolo, Asia Spinelli, Domenica Scordamaglia, Lucia Muglia, Rita Guzzi, Anna Maria Miglietta, Ernestina Marianna De Francesco, Antonino Belfiore, Marcello Maggiolini, Rosamaria Lappano
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	breast cancer ERα46 estrogens insulin insulin receptor Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/1f8643db7ad8465e9ea13f2b11edef84
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spelling	oai:doaj.org-article:1f8643db7ad8465e9ea13f2b11edef842021-11-30T07:25:37ZEstrogen receptor variant ERα46 and insulin receptor drive in primary breast cancer cells growth effects and interleukin 11 induction prompting the motility of cancer‐associated fibroblasts2001-132610.1002/ctm2.516https://doaj.org/article/1f8643db7ad8465e9ea13f2b11edef842021-11-01T00:00:00Zhttps://doi.org/10.1002/ctm2.516https://doaj.org/toc/2001-1326Abstract Among the prognostic and predictive biomarkers of breast cancer (BC), the role of estrogen receptor (ER)α wild‐type has been acknowledged, although the action of certain ERα splice variants has not been elucidated. Insulin/insulin receptor (IR) axis has also been involved in the progression and metastasis of BC. For instance, hyperinsulinemia, which is often associated with obesity and type 2 diabetes, may be a risk factor for BC. Similarly, an aberrant expression of IR or its hyperactivation may correlate with aggressive BC phenotypes. In the present study, we have shown that a novel naturally immortalized BC cell line (named BCAHC‐1) is characterized by a unique expression of 46 kDa ERα splice variant (ERα46) along with IR. Moreover, we have shown that a multifaceted crosstalk between ERα46 and IR occurs in BCAHC‐1 cells upon estrogen and insulin exposure for growth and pulmonary metastasis. Through high‐throughput RNA sequencing analysis, we have also found that the cytokine interleukin‐11 (IL11) is the main factor linking BCAHC‐1 cells to breast cancer‐associated fibroblasts (CAFs). In particular, we have found that IL11 induced by estrogens and insulin in BCAHC‐1 cells regulates pro‐tumorigenic genes of the “extracellular matrix organization” signaling pathway, such as ICAM‐1 and ITGA5, and promotes both migratory and invasive features in breast CAFs. Overall, our results may open a new scientific avenue to identify additional prognostic and therapeutic targets in BC.Francesca CirilloMichele PellegrinoMarianna TaliaIda Daniela PerrottaDamiano Cosimo RigiraccioloAsia SpinelliDomenica ScordamagliaLucia MugliaRita GuzziAnna Maria MigliettaErnestina Marianna De FrancescoAntonino BelfioreMarcello MaggioliniRosamaria LappanoWileyarticlebreast cancerERα46estrogensinsulininsulin receptorMedicine (General)R5-920ENClinical and Translational Medicine, Vol 11, Iss 11, Pp n/a-n/a (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	breast cancer ERα46 estrogens insulin insulin receptor Medicine (General) R5-920
spellingShingle	breast cancer ERα46 estrogens insulin insulin receptor Medicine (General) R5-920 Francesca Cirillo Michele Pellegrino Marianna Talia Ida Daniela Perrotta Damiano Cosimo Rigiracciolo Asia Spinelli Domenica Scordamaglia Lucia Muglia Rita Guzzi Anna Maria Miglietta Ernestina Marianna De Francesco Antonino Belfiore Marcello Maggiolini Rosamaria Lappano Estrogen receptor variant ERα46 and insulin receptor drive in primary breast cancer cells growth effects and interleukin 11 induction prompting the motility of cancer‐associated fibroblasts
description	Abstract Among the prognostic and predictive biomarkers of breast cancer (BC), the role of estrogen receptor (ER)α wild‐type has been acknowledged, although the action of certain ERα splice variants has not been elucidated. Insulin/insulin receptor (IR) axis has also been involved in the progression and metastasis of BC. For instance, hyperinsulinemia, which is often associated with obesity and type 2 diabetes, may be a risk factor for BC. Similarly, an aberrant expression of IR or its hyperactivation may correlate with aggressive BC phenotypes. In the present study, we have shown that a novel naturally immortalized BC cell line (named BCAHC‐1) is characterized by a unique expression of 46 kDa ERα splice variant (ERα46) along with IR. Moreover, we have shown that a multifaceted crosstalk between ERα46 and IR occurs in BCAHC‐1 cells upon estrogen and insulin exposure for growth and pulmonary metastasis. Through high‐throughput RNA sequencing analysis, we have also found that the cytokine interleukin‐11 (IL11) is the main factor linking BCAHC‐1 cells to breast cancer‐associated fibroblasts (CAFs). In particular, we have found that IL11 induced by estrogens and insulin in BCAHC‐1 cells regulates pro‐tumorigenic genes of the “extracellular matrix organization” signaling pathway, such as ICAM‐1 and ITGA5, and promotes both migratory and invasive features in breast CAFs. Overall, our results may open a new scientific avenue to identify additional prognostic and therapeutic targets in BC.
format	article
author	Francesca Cirillo Michele Pellegrino Marianna Talia Ida Daniela Perrotta Damiano Cosimo Rigiracciolo Asia Spinelli Domenica Scordamaglia Lucia Muglia Rita Guzzi Anna Maria Miglietta Ernestina Marianna De Francesco Antonino Belfiore Marcello Maggiolini Rosamaria Lappano
author_facet	Francesca Cirillo Michele Pellegrino Marianna Talia Ida Daniela Perrotta Damiano Cosimo Rigiracciolo Asia Spinelli Domenica Scordamaglia Lucia Muglia Rita Guzzi Anna Maria Miglietta Ernestina Marianna De Francesco Antonino Belfiore Marcello Maggiolini Rosamaria Lappano
author_sort	Francesca Cirillo
title	Estrogen receptor variant ERα46 and insulin receptor drive in primary breast cancer cells growth effects and interleukin 11 induction prompting the motility of cancer‐associated fibroblasts
title_short	Estrogen receptor variant ERα46 and insulin receptor drive in primary breast cancer cells growth effects and interleukin 11 induction prompting the motility of cancer‐associated fibroblasts
title_full	Estrogen receptor variant ERα46 and insulin receptor drive in primary breast cancer cells growth effects and interleukin 11 induction prompting the motility of cancer‐associated fibroblasts
title_fullStr	Estrogen receptor variant ERα46 and insulin receptor drive in primary breast cancer cells growth effects and interleukin 11 induction prompting the motility of cancer‐associated fibroblasts
title_full_unstemmed	Estrogen receptor variant ERα46 and insulin receptor drive in primary breast cancer cells growth effects and interleukin 11 induction prompting the motility of cancer‐associated fibroblasts
title_sort	estrogen receptor variant erα46 and insulin receptor drive in primary breast cancer cells growth effects and interleukin 11 induction prompting the motility of cancer‐associated fibroblasts
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/1f8643db7ad8465e9ea13f2b11edef84
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Estrogen receptor variant ERα46 and insulin receptor drive in primary breast cancer cells growth effects and interleukin 11 induction prompting the motility of cancer‐associated fibroblasts

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