Excess Endocrine Growth Hormone in Acromegaly Promotes the Aggressiveness and Metastasis of Triple-negative Breast Cancer

Overview

Journal iScience

Publisher Cell Press

Date 2024 Jul 15

PMID 39006481

Authors

Chan Woo Kang

Ju Hun Oh

Eun Kyung Wang

Yaru Bao

Ye Bin Kim

Min-Ho Lee

Yang Jong Lee

Young Seok Jo

Cheol Ryong Ku

Eun Jig Lee

Affiliations

Soon will be listed here.

Abstract

Pituitary adenoma-induced excess endocrine growth hormone (GH) secretion can lead to breast cancer development and metastasis. Herein, we used an acromegaly mouse model to investigate the role of excess endocrine GH on triple-negative breast cancer (TNBC) growth and metastasis. Additionally, we aimed to elucidate the molecular mechanism of transcription factor 20 (TCF20)/nuclear factor erythroid 2-related factor 2 (NRF2) signaling-mediated aggressiveness and metastasis of TNBC. Excess endocrine GH induced TCF20 activates the transcription of and NRF2-target genes to facilitate TNBC metastasis. Inhibition of GH receptor (GHR) and TCF20 activity using the GHR antagonist or small-interfering RNA-induced gene knockdown resulted in reduced tumor volume and metastasis, suggesting that excess endocrine GH stimulates TCF20/NRF2 pathways in TNBC and promotes metastasis to the lung. GHR inhibitors present an effective therapeutic strategy to prevent TNBC cell growth and metastasis. Our findings revealed functional and mechanistic roles of the GH-TCF20-NRF2 signaling axis in TBNC progression.

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