Cited 2 time in webofscience Cited 4 time in scopus

Extracellular Acidosis Promotes Metastatic Potency via Decrease of the BMAL1 Circadian Clock Gene in Breast Cancer

Title
Extracellular Acidosis Promotes Metastatic Potency via Decrease of the BMAL1 Circadian Clock Gene in Breast Cancer
Authors
Kwon, Yong-JinSeo, Eun-BiKwon, Sun-HoLee, Song-HeeKim, Seul-KiPark, Sang KiKim, KyungjinPark, SaeGwangPark, In-ChulPark, Jong-WanYe, Sang-Kyu
DGIST Authors
Kwon, Yong-Jin; Seo, Eun-Bi; Kwon, Sun-Ho; Lee, Song-Hee; Kim, Seul-Ki; Park, Sang Ki; Kim, Kyungjin; Park, SaeGwang; Park, In-Chul; Park, Jong-Wan; Ye, Sang-Kyu
Issue Date
2020-04
Citation
Cells, 9(4), 989
Type
Article
Article Type
Article
Author Keywords
circadian clockBMAL1hypoxiaacidosisbreast cancermetastasis
Keywords
TUMOR PROGRESSIONEPITHELIAL-CELLSMELATONINHYPOXIAPHANGIOGENESISOSCILLATIONSENSITIVITYINVASIONDRIVERS
ISSN
2073-4409
Abstract
Circadian oscillation is an essential process that influences many physiological and biological mechanisms and a decrease of circadian genes is associated with many diseases such as cancer. Despite many efforts to identify the detailed mechanism for decreasing circadian genes and recovering reduced circadian genes in cancer, it is still largely unknown. We found that BMAL1 was reduced in tumor hypoxia-induced acidosis, and recovered by selectively targeting acidic pH in breast cancer cell lines. Surprisingly, BMAL1 was reduced by decrease of protein stability as well as inhibition of transcription under acidosis. In addition, melatonin significantly prevented acidosis-mediated decrease of BMAL1 by inhibiting lactate dehydrogenase-A during hypoxia. Remarkably, acidosis-mediated metastasis was significantly alleviated by BMAL1 overexpression in breast cancer cells. We therefore suggest that tumor hypoxia-induced acidosis promotes metastatic potency by decreasing BMAL1, and that tumor acidosis could be a target for preventing breast cancer metastasis by sustaining BMAL1.
URI
http://hdl.handle.net/20.500.11750/12052
DOI
10.3390/cells9040989
Publisher
MDPI
Files:
Collection:


qrcode mendeley

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE