Neuregulin 4 Boosts the Efficacy of Anti-ERBB2 Neutralizing Antibodies.
ERBB2 (HER2)
HER2+ breast cancer
HER2-targeted agents
breast cancer
neuregulin 1 (NRG1)
neuregulin 4 (NRG4)
pertuzumab (Perjeta)
trastuzumab (Herceptin)
Journal
Frontiers in oncology
ISSN: 2234-943X
Titre abrégé: Front Oncol
Pays: Switzerland
ID NLM: 101568867
Informations de publication
Date de publication:
2022
2022
Historique:
received:
08
12
2021
accepted:
01
04
2022
entrez:
6
6
2022
pubmed:
7
6
2022
medline:
7
6
2022
Statut:
epublish
Résumé
ERBB4 is a tyrosine kinase receptor reported to exert both oncogenic and tumor suppressor activities. These paradoxical effects were suggested to stem from different ERBB4 homo-/hetero-dimers and/or isoforms. By stratifying breast cancer patients for clinical and molecular subtypes and ERBB4 mRNA abundance, we here report that higher ERBB4 levels correlate with longer relapse-free survival in breast cancer patients of HER2-enriched and luminal A molecular subtypes, proposing a cancer-protecting role for this receptor in these specific subgroups. We also observed that HER2-enriched breast cancers express intermediate ERBB4 mRNA levels compared to luminal and triple-negative/basal-like subgroups, which displayed the highest and the lowest levels, respectively. Inspired by these clinical data, we tested the activation of ERBB4 by Neuregulins as a potential anticancer strategy for HER2+ breast cancers. To this end, we employed two HER2+ breast cancer cellular models (BT474 and SKBR3), which express intermediate/high and low ERBB4 levels, respectively. Cell proliferation and motility were evaluated on these cellular models following treatments with Neuregulin 1 (NRG1), which activates both ERBB3 and ERBB4, or Neuregulin 4 (NRG4), which specifically activates ERBB4. Both NRG1 and NRG4 were used alone or in combination with anti-ERBB2 neutralizing antibodies, namely trastuzumab and pertuzumab.
Identifiants
pubmed: 35664762
doi: 10.3389/fonc.2022.831105
pmc: PMC9157648
doi:
Types de publication
Journal Article
Langues
eng
Pagination
831105Informations de copyright
Copyright © 2022 Miano, Romaniello, Mazzeschi, Morselli, Da Pra, Sacchi, Bongiovanni, Sgarzi, Pantano, Lauriola and D’Uva.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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