Stabilization of IGF2BP1 by USP10 promotes breast cancer metastasis via CPT1A in an m6A-dependent manner

Shi, Jiajun; Zhang, Qianyi; Yin, Xi; Ye, Jiahui; Gao, Shengqing; Chen, Chen; Yang, Yaxuan; Wu, Baojuan; Fu, Yuping; Zhang, Hongmei; Wang, Zhangding; Wang, Bo; Zhu, Yun; Wu, Hongyan; Yao, Yongzhong; Xu, Guifang; Wang, Qiang; Wang, Shouyu; Zhang, Weijie

doi:10.7150/ijbs.76798

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Theranostics

International Journal of Medical Sciences

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Journal of Cancer

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Int J Biol Sci 2023; 19(2):449-464. doi:10.7150/ijbs.76798 This issue Cite

Research Paper

Stabilization of IGF2BP1 by USP10 promotes breast cancer metastasis via CPT1A in an m6A-dependent manner

Jiajun Shi^1*, Qianyi Zhang^2*, Xi Yin^1*, Jiahui Ye^1*, Shengqing Gao³, Chen Chen², Yaxuan Yang¹, Baojuan Wu¹, Yuping Fu⁴, Hongmei Zhang⁴, Zhangding Wang⁶, Bo Wang⁷, Yun Zhu⁶, Hongyan Wu⁵, Yongzhong Yao¹, Guifang Xu^6✉, Qiang Wang^8✉, Shouyu Wang^2,7,9✉, Weijie Zhang^1✉

1. Department of General Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210000, Jiangsu Province, People's Republic of China.
2. Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210000, Jiangsu Province, People's Republic of China.
3. Department of Neurosurgery, Jinling Hospital, Medical School of Nanjing University, Nanjing 210000, Jiangsu Province, People's Republic of China.
4. Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210000, Jiangsu Province, People's Republic of China.
5. Department of Pathology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210000, Jiangsu Province, People's Republic of China.
6. Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210000, Jiangsu Province, People's Republic of China.
7. Department of Hepatobiliary Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210000, Jiangsu Province, People's Republic of China.
8. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui Province, People's Republic of China.
9. Center for Public Health Research, Medical School of Nanjing University, Nanjing 210000, Jiangsu Province, People's Republic of China.
*These authors contributed equally to this work.

Citation:

Shi J, Zhang Q, Yin X, Ye J, Gao S, Chen C, Yang Y, Wu B, Fu Y, Zhang H, Wang Z, Wang B, Zhu Y, Wu H, Yao Y, Xu G, Wang Q, Wang S, Zhang W. Stabilization of IGF2BP1 by USP10 promotes breast cancer metastasis via CPT1A in an m6A-dependent manner. Int J Biol Sci 2023; 19(2):449-464. doi:10.7150/ijbs.76798. https://www.ijbs.com/v19p0449.htm

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Abstract

Metastasis leads to the vast majority of breast cancer mortality. Increasing evidence has shown that N6-methyladenosine (m6A) modification and its associated regulators play a pivotal role in breast cancer metastasis. Here, we showed that overexpression of the m6A reader IGF2BP1 was clinically correlated with metastasis in breast cancer patients. Moreover, IGF2BP1 promoted distant metastasis in vitro and in vivo. Mechanistically, we first identified USP10 as the IGF2BP1 deubiquitinase. USP10 can bind to, deubiquitinate, and stabilize IGF2BP1, resulting in its higher expression level in breast cancer. Furthermore, by MeRIP-seq and experimental verification, we found that IGF2BP1 directly recognized and bound to the m6A sites on CPT1A mRNA and enhanced its stability, which ultimately mediated IGF2BP1-induced breast cancer metastasis. In clinical samples, USP10 levels correlated with IGF2BP1 and CPT1A levels, and breast cancer patients with high levels of USP10, IGF2BP1, and CPT1A had the worst outcome. Therefore, these findings suggest that the USP10/IGF2BP1/CPT1A axis facilitates breast cancer metastasis, and this axis may be a promising prognostic biomarker and therapeutic target for breast cancer.

Keywords: Breast cancer, metastasis, m6A, IGF2BP1, USP10, CPT1A

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APA

Shi, J., Zhang, Q., Yin, X., Ye, J., Gao, S., Chen, C., Yang, Y., Wu, B., Fu, Y., Zhang, H., Wang, Z., Wang, B., Zhu, Y., Wu, H., Yao, Y., Xu, G., Wang, Q., Wang, S., Zhang, W. (2023). Stabilization of IGF2BP1 by USP10 promotes breast cancer metastasis via CPT1A in an m6A-dependent manner. International Journal of Biological Sciences, 19(2), 449-464. https://doi.org/10.7150/ijbs.76798.

ACS

Shi, J.; Zhang, Q.; Yin, X.; Ye, J.; Gao, S.; Chen, C.; Yang, Y.; Wu, B.; Fu, Y.; Zhang, H.; Wang, Z.; Wang, B.; Zhu, Y.; Wu, H.; Yao, Y.; Xu, G.; Wang, Q.; Wang, S.; Zhang, W. Stabilization of IGF2BP1 by USP10 promotes breast cancer metastasis via CPT1A in an m6A-dependent manner. Int. J. Biol. Sci. 2023, 19 (2), 449-464. DOI: 10.7150/ijbs.76798.

NLM

CSE

Shi J, Zhang Q, Yin X, Ye J, Gao S, Chen C, Yang Y, Wu B, Fu Y, Zhang H, Wang Z, Wang B, Zhu Y, Wu H, Yao Y, Xu G, Wang Q, Wang S, Zhang W. 2023. Stabilization of IGF2BP1 by USP10 promotes breast cancer metastasis via CPT1A in an m6A-dependent manner. Int J Biol Sci. 19(2):449-464.

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