Journal
ONCOGENE
Volume 39, Issue 12, Pages 2550-2567Publisher
SPRINGERNATURE
DOI: 10.1038/s41388-020-1165-z
Keywords
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Funding
- National Natural Science Foundation of China [81672912, 81972753, 81502537]
- Science and Technology Program of Guangdong Province, China [2017B030301016, 2016A030310128]
- Shenzhen Basic Research Program [JCYJ20170818143630465, JCYJ20170818101638620, JCYJ20180507182203049]
- Shenzhen Peacock Innovation Team Project [KQTD20140630100658078]
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Aurora B is a serine/threonine kinase that has been implicated in regulating cell proliferation in distinct cancers, including breast cancer. Here we show that Aurora B expression is elevated in basal-like breast cancer (BLBC) compared with other breast cancer subtypes. This high level of expression seems to correlate with poor metastasis-free survival and relapse-free survival in affected patients. Mechanistically, we show that elevated Aurora B expression in breast cancer cells activates AKT/GSK3 beta to stabilize Snail1 protein, a master regulator of epithelial-mesenchymal transition (EMT), leading to EMT induction in a kinase-dependent manner. Conversely, Aurora B knock down by short-hairpin RNAs (shRNAs) suppresses AKT/GSK3 beta/Snail1 signaling, reverses EMT and reduces breast cancer metastatic potential in vitro and in vivo. Finally, we identified a specific OCT4 phosphorylation site (T343) responsible for mediating Aurora B-induced AKT/GSK3 beta/Snail1 signaling and EMT that could be attenuated by Aurora B kinase inhibitor treatment. These findings support that Aurora B induces EMT to promote breast cancer metastasis via OCT4/AKT/GSK3 beta/Snail1 signaling. Pharmacologic Aurora B inhibition might be a potential effective treatment for breast cancer patients with metastatic disease.
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