The role of HER2 and HER3 in HER2-amplified cancers beyond breast cancers

Abstract HER2 and HER3 play key driving functions in the pathophysiology of HER2-amplified breast cancers, but this function is less well characterized in other cancers driven by HER2 amplification. This study aimed to explore the role of HER2 and HER3 signaling in other types of HER2-amplified canc...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Avisek Majumder, Manbir Sandhu, Debarko Banerji, Veronica Steri, Adam Olshen, Mark M. Moasser
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c397830c5fdc4bd9aad3949e664aac3c
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:c397830c5fdc4bd9aad3949e664aac3c
record_format	dspace
spelling	oai:doaj.org-article:c397830c5fdc4bd9aad3949e664aac3c2021-12-02T13:41:34ZThe role of HER2 and HER3 in HER2-amplified cancers beyond breast cancers10.1038/s41598-021-88683-w2045-2322https://doaj.org/article/c397830c5fdc4bd9aad3949e664aac3c2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88683-whttps://doaj.org/toc/2045-2322Abstract HER2 and HER3 play key driving functions in the pathophysiology of HER2-amplified breast cancers, but this function is less well characterized in other cancers driven by HER2 amplification. This study aimed to explore the role of HER2 and HER3 signaling in other types of HER2-amplified cancer. The expression and signaling activity of HER2, HER3, and downstream pathway proteins were studied in cell panels representing HER2-amplified cancers of the breast, bladder, colon and rectal, stomach, esophagus, lung, tongue, and endometrium along with controls lacking HER2 amplification. We report that HER2-amplified cancers are addicted to HER2 across different cancer types and the depth of addiction is best linked with the expression level of HER2, but not with HER3 expression. We report that the expression and constitutive phosphorylation of HER3 are ubiquitous in HER2-amplified breast cancer cell lines, but much more variable in HER2-amplified cancer cells from other tissues. We observed the lapatinib-induced compensatory upregulation of HER3 signaling in many types of HER2-amplified cancers, although with much variability. We find that HER3 expression is essential for in vivo tumorigenic growth in some HER2-amplified tumors but not others. Importantly HER3 expression level does not correlate well with its functional importance. More biomarkers will be needed to guide the optimal use of HER3 inhibitors in HER2-amplified cancers from non-breast origin. Unlike oncogenes activated through mutational events, the activation of HER2 through overexpression represents a gradient of activities and depth of addiction and the response to inhibitors follows a similar gradient.Avisek MajumderManbir SandhuDebarko BanerjiVeronica SteriAdam OlshenMark M. MoasserNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Avisek Majumder Manbir Sandhu Debarko Banerji Veronica Steri Adam Olshen Mark M. Moasser The role of HER2 and HER3 in HER2-amplified cancers beyond breast cancers
description	Abstract HER2 and HER3 play key driving functions in the pathophysiology of HER2-amplified breast cancers, but this function is less well characterized in other cancers driven by HER2 amplification. This study aimed to explore the role of HER2 and HER3 signaling in other types of HER2-amplified cancer. The expression and signaling activity of HER2, HER3, and downstream pathway proteins were studied in cell panels representing HER2-amplified cancers of the breast, bladder, colon and rectal, stomach, esophagus, lung, tongue, and endometrium along with controls lacking HER2 amplification. We report that HER2-amplified cancers are addicted to HER2 across different cancer types and the depth of addiction is best linked with the expression level of HER2, but not with HER3 expression. We report that the expression and constitutive phosphorylation of HER3 are ubiquitous in HER2-amplified breast cancer cell lines, but much more variable in HER2-amplified cancer cells from other tissues. We observed the lapatinib-induced compensatory upregulation of HER3 signaling in many types of HER2-amplified cancers, although with much variability. We find that HER3 expression is essential for in vivo tumorigenic growth in some HER2-amplified tumors but not others. Importantly HER3 expression level does not correlate well with its functional importance. More biomarkers will be needed to guide the optimal use of HER3 inhibitors in HER2-amplified cancers from non-breast origin. Unlike oncogenes activated through mutational events, the activation of HER2 through overexpression represents a gradient of activities and depth of addiction and the response to inhibitors follows a similar gradient.
format	article
author	Avisek Majumder Manbir Sandhu Debarko Banerji Veronica Steri Adam Olshen Mark M. Moasser
author_facet	Avisek Majumder Manbir Sandhu Debarko Banerji Veronica Steri Adam Olshen Mark M. Moasser
author_sort	Avisek Majumder
title	The role of HER2 and HER3 in HER2-amplified cancers beyond breast cancers
title_short	The role of HER2 and HER3 in HER2-amplified cancers beyond breast cancers
title_full	The role of HER2 and HER3 in HER2-amplified cancers beyond breast cancers
title_fullStr	The role of HER2 and HER3 in HER2-amplified cancers beyond breast cancers
title_full_unstemmed	The role of HER2 and HER3 in HER2-amplified cancers beyond breast cancers
title_sort	role of her2 and her3 in her2-amplified cancers beyond breast cancers
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c397830c5fdc4bd9aad3949e664aac3c
work_keys_str_mv	AT avisekmajumder theroleofher2andher3inher2amplifiedcancersbeyondbreastcancers AT manbirsandhu theroleofher2andher3inher2amplifiedcancersbeyondbreastcancers AT debarkobanerji theroleofher2andher3inher2amplifiedcancersbeyondbreastcancers AT veronicasteri theroleofher2andher3inher2amplifiedcancersbeyondbreastcancers AT adamolshen theroleofher2andher3inher2amplifiedcancersbeyondbreastcancers AT markmmoasser theroleofher2andher3inher2amplifiedcancersbeyondbreastcancers AT avisekmajumder roleofher2andher3inher2amplifiedcancersbeyondbreastcancers AT manbirsandhu roleofher2andher3inher2amplifiedcancersbeyondbreastcancers AT debarkobanerji roleofher2andher3inher2amplifiedcancersbeyondbreastcancers AT veronicasteri roleofher2andher3inher2amplifiedcancersbeyondbreastcancers AT adamolshen roleofher2andher3inher2amplifiedcancersbeyondbreastcancers AT markmmoasser roleofher2andher3inher2amplifiedcancersbeyondbreastcancers
_version_	1718392579698982912

The role of HER2 and HER3 in HER2-amplified cancers beyond breast cancers

Ejemplares similares