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Theranostics 2021; 11(13):6592-6606. doi:10.7150/thno.59816 This issue Cite

Research Paper

Targeting hyperactive TGFBR2 for treating MYOCD deficient lung cancer

Qian Zhou1✉*, Wensheng Chen1*, Zhenzhen Fan1*, Zhipeng Chen1*, Jinxia Liang1*, Guandi Zeng1, Lu Liu1, Wanting Liu1, Tong Yang1, Xin Cao2, Biao Yu3, Meng Xu4, Ye-Guang Chen5,6✉, Liang Chen1✉

1. MOE Key Laboratory of Tumor Molecular Biology and Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou 510632, China.
2. Zhongshan Hospital, Institute of Clinical Science, Fudan University Shanghai Medical College, 180 Fengling Road, Shanghai, 200032, China.
3. State Key Laboratory of Bioorganic and Natural Products Chemistry, Center for Excellence in Molecular Synthesis, Shanghai, Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032, China.
4. Department of Oncology, The First Affiliated Hospital, Jinan University, Guangzhou 510632, China.
5. The State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.
6. Max-Planck Center for Tissue Stem Cell Research and Regenerative Medicine, Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, China.
*These authors contributed equally to this work.

✉ Corresponding authors: Qian Zhou, Telephone: (086)-020-8522-6223, E-mail: zhouqian_whucom; Ye-Guang Chen, Telephone: (086)-010-6278-4794, E-mail: ygchenedu.cn; Liang Chen, Telephone: (086)-020-8522-2875, E-mail: chenliangedu.cn.

Citation:
Zhou Q, Chen W, Fan Z, Chen Z, Liang J, Zeng G, Liu L, Liu W, Yang T, Cao X, Yu B, Xu M, Chen YG, Chen L. Targeting hyperactive TGFBR2 for treating MYOCD deficient lung cancer. Theranostics 2021; 11(13):6592-6606. doi:10.7150/thno.59816. https://www.thno.org/v11p6592.htm
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Abstract

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Purpose: Clinical success of cancer therapy is severely limited by drug resistance, attributed in large part to the loss of function of tumor suppressor genes (TSGs). Developing effective strategies to treat those tumors is challenging, but urgently needed in clinic.

Experimental Design: MYOCD is a clinically relevant TSG in lung cancer patients. Our in vitro and in vivo data confirm its tumor suppressive function. Further analysis reveals that MYOCD potently inhibits stemness of lung cancer stem cells. Mechanistically, MYOCD localizes to TGFBR2 promoter region and thereby recruits PRMT5/MEP50 complex to epigenetically silence its transcription.

Conclusions: NSCLC cells deficient of MYOCD are particularly sensitive to TGFBR kinase inhibitor (TGFBRi). TGFBRi and stemness inhibitor synergize with existing drugs to treat MYOCD deficient lung cancers. Our current work shows that loss of function of MYOCD creates Achilles' heels in lung cancer cells, which might be exploited in clinic.

Keywords: tumor suppressor gene, targeted therapy, drug resistance

Citation styles

APA
Zhou, Q., Chen, W., Fan, Z., Chen, Z., Liang, J., Zeng, G., Liu, L., Liu, W., Yang, T., Cao, X., Yu, B., Xu, M., Chen, Y.G., Chen, L. (2021). Targeting hyperactive TGFBR2 for treating MYOCD deficient lung cancer. Theranostics, 11(13), 6592-6606. https://doi.org/10.7150/thno.59816.

ACS
Zhou, Q.; Chen, W.; Fan, Z.; Chen, Z.; Liang, J.; Zeng, G.; Liu, L.; Liu, W.; Yang, T.; Cao, X.; Yu, B.; Xu, M.; Chen, Y.G.; Chen, L. Targeting hyperactive TGFBR2 for treating MYOCD deficient lung cancer. Theranostics 2021, 11 (13), 6592-6606. DOI: 10.7150/thno.59816.

NLM
Zhou Q, Chen W, Fan Z, Chen Z, Liang J, Zeng G, Liu L, Liu W, Yang T, Cao X, Yu B, Xu M, Chen YG, Chen L. Targeting hyperactive TGFBR2 for treating MYOCD deficient lung cancer. Theranostics 2021; 11(13):6592-6606. doi:10.7150/thno.59816. https://www.thno.org/v11p6592.htm

CSE
Zhou Q, Chen W, Fan Z, Chen Z, Liang J, Zeng G, Liu L, Liu W, Yang T, Cao X, Yu B, Xu M, Chen YG, Chen L. 2021. Targeting hyperactive TGFBR2 for treating MYOCD deficient lung cancer. Theranostics. 11(13):6592-6606.

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