Beauvericin suppresses the proliferation and pulmonary metastasis of osteosarcoma by selectively inhibiting TGFBR2 pathway

Ye, Geni; Jiao, Yubo; Deng, Lijuan; Cheng, Minjing; Wang, Sheng; Zhang, Junqiu; Ouyang, Jie; Li, Yong; He, Yuxin; Tu, Zhengchao; Wang, Zhen; Song, Xiaojuan; Wang, Chenran; Qi, Qi; Zhang, Dongmei; Wang, Lei; Huang, Maohua; Ye, Wencai; Chen, Minfeng

doi:10.7150/ijbs.86214

Theranostics

International Journal of Medical Sciences

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Journal of Cancer

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Int J Biol Sci 2023; 19(14):4376-4392. doi:10.7150/ijbs.86214 This issue Cite

Research Paper

Beauvericin suppresses the proliferation and pulmonary metastasis of osteosarcoma by selectively inhibiting TGFBR2 pathway

Geni Ye^1,2*, Yubo Jiao^1,2*, Lijuan Deng^3*, Minjing Cheng^1,2, Sheng Wang^1,2, Junqiu Zhang^1,2, Jie Ouyang^1,2, Yong Li¹, Yuxin He¹, Zhengchao Tu¹, Zhen Wang¹, Xiaojuan Song¹, Chenran Wang^1,2, Qi Qi⁴, Dongmei Zhang^1,2, Lei Wang^1,2✉, Maohua Huang^1,2✉, Wencai Ye^1,2✉, Minfeng Chen^1,2,5✉

1. State Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, Guangzhou, 510632, China.
2. Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou, 510632, China.
3. Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, Jinan University, Guangzhou, 510632, China.
4. MOE Key Laboratory of Tumor Molecular Biology, Clinical Translational Center for Targeted Drug, Department of Pharmacology, School of Medicine, Jinan University, Guangzhou, 510632, China.
5. State Key Laboratory of Chemical Oncogenomics, Guangdong Provincial Key Laboratory of Chemical Biology, Tsinghua Shenzhen International Graduate School, Shenzhen, 518055, China.
* These authors contributed equally to this study.

Citation:

Ye G, Jiao Y, Deng L, Cheng M, Wang S, Zhang J, Ouyang J, Li Y, He Y, Tu Z, Wang Z, Song X, Wang C, Qi Q, Zhang D, Wang L, Huang M, Ye W, Chen M. Beauvericin suppresses the proliferation and pulmonary metastasis of osteosarcoma by selectively inhibiting TGFBR2 pathway. Int J Biol Sci 2023; 19(14):4376-4392. doi:10.7150/ijbs.86214. https://www.ijbs.com/v19p4376.htm

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Abstract

Osteosarcoma (OS) patients, particularly those with distant metastasis, experience rapid progression and derive poor survival benefits from traditional therapies. Currently, effective drugs for treating patients with metastatic OS remain scarce. Here, we found that the cyclic hexadepsipeptide beauvericin (BEA) functioned as a new selective TGFBR2 inhibitor with potent antiproliferative and antimetastatic activities against OS cells. Functionally, BEA inhibited TGF-β signaling-mediated proliferation, invasiveness, mesenchymal phenotype, and extracellular matrix remodeling of OS cells, and suppressed tumor growth and reduced pulmonary metastasis in vivo. Mechanistic investigation revealed that BEA selectively and directly bound to Asn 332 of TGFBR2 and inhibited its kinase activity, thereby suppressing the aggressive progression of OS cells. Together, our study identifies an innovative and natural selective TGFBR2 inhibitor with effective antineoplastic activity against metastatic OS and demonstrates that targeting TGFBR2 could be a potential therapeutic strategy for metastatic OS.

Keywords: beauvericin, osteosarcoma, proliferation, pulmonary metastasis, TGF-β, TGFBR2

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APA

Ye, G., Jiao, Y., Deng, L., Cheng, M., Wang, S., Zhang, J., Ouyang, J., Li, Y., He, Y., Tu, Z., Wang, Z., Song, X., Wang, C., Qi, Q., Zhang, D., Wang, L., Huang, M., Ye, W., Chen, M. (2023). Beauvericin suppresses the proliferation and pulmonary metastasis of osteosarcoma by selectively inhibiting TGFBR2 pathway. International Journal of Biological Sciences, 19(14), 4376-4392. https://doi.org/10.7150/ijbs.86214.

ACS

Ye, G.; Jiao, Y.; Deng, L.; Cheng, M.; Wang, S.; Zhang, J.; Ouyang, J.; Li, Y.; He, Y.; Tu, Z.; Wang, Z.; Song, X.; Wang, C.; Qi, Q.; Zhang, D.; Wang, L.; Huang, M.; Ye, W.; Chen, M. Beauvericin suppresses the proliferation and pulmonary metastasis of osteosarcoma by selectively inhibiting TGFBR2 pathway. Int. J. Biol. Sci. 2023, 19 (14), 4376-4392. DOI: 10.7150/ijbs.86214.

NLM

CSE

Ye G, Jiao Y, Deng L, Cheng M, Wang S, Zhang J, Ouyang J, Li Y, He Y, Tu Z, Wang Z, Song X, Wang C, Qi Q, Zhang D, Wang L, Huang M, Ye W, Chen M. 2023. Beauvericin suppresses the proliferation and pulmonary metastasis of osteosarcoma by selectively inhibiting TGFBR2 pathway. Int J Biol Sci. 19(14):4376-4392.

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