Int J Biol Sci 2022; 18(6):2452-2471. doi:10.7150/ijbs.69134 This issue

Research Paper

USF1-ATRAP-PBX3 Axis Promote Breast Cancer Glycolysis and Malignant Phenotype by Activating AKT/mTOR Signaling

Dandan Wang1*, Xiaoying Jin1*, Mengxia Lei1*, Ying Jiang2, Yali Liu1, Fei Yu1, Yan Guo1, Bing Han1, Yue Yang3,4, Weiling Sun5, Ying Liu5, Guangchun Zeng6, Feng Liu7✉, Jing Hu1✉, Xuesong Chen1✉

1. Department of Breast Medical Oncology, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin 150040, China
2. Department of Biochemistry and Molecular Biology, Mudanjiang Medical University, 3 Tongxiang Street, Mudanjang 157011, China
3. Heilongjiang Academy of Medical Sciences, Harbin Medical University, 157 Baojian Road, Harbin 150081, China
4. The Institute of Cancer Prevention and Treatment, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin 150040, China
5. Department of Medical Oncology, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin 150040, China
6. Department of Pathology, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin 150040, China
7. Department of Breast Surgery, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin 150040, China
*These authors contributed equally: Dandan Wang, Xiaoying Jin, and Mengxia Lei

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Citation:
Wang D, Jin X, Lei M, Jiang Y, Liu Y, Yu F, Guo Y, Han B, Yang Y, Sun W, Liu Y, Zeng G, Liu F, Hu J, Chen X. USF1-ATRAP-PBX3 Axis Promote Breast Cancer Glycolysis and Malignant Phenotype by Activating AKT/mTOR Signaling. Int J Biol Sci 2022; 18(6):2452-2471. doi:10.7150/ijbs.69134. Available from https://www.ijbs.com/v18p2452.htm

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Abstract

Graphic abstract

Angiotensin II type 1 receptor-associated protein (ATRAP) is widely expressed in different tissues and organs, although its mechanistic role in breast cancer remains unclear. Here, we show that ATRAP is highly expressed in breast cancer tissues. Its aberrant upregulation promotes breast cancer aggressiveness and is positively correlated with poor prognosis. Functional assays revealed that ATRAP participates in promoting cell growth, metastasis, and aerobic glycolysis, while microarray analysis showed that ATRAP can activate the AKT/mTOR signaling pathway in cancer progression. In addition, ATRAP was revealed to direct Ubiquitin-specific protease 14 (USP14)-mediated deubiquitination and stabilization of Pre-B cell leukemia homeobox 3 (PBX3). Importantly, ATRAP is a direct target of Upstream stimulatory factor 1 (USF1), and that ATRAP overexpression reverses the inhibitory effects of USF1 knockdown. Our study demonstrates the broad contribution of the USF1/ATRAP/PBX3 axis to breast cancer progression and provides a strong potential therapeutic target.

Keywords: Breast cancer, ATRAP, Glycolytic metabolism, AKT/mTOR signaling, Ubiquitination