Int J Biol Sci 2022; 18(16):6163-6175. doi:10.7150/ijbs.78354 This issue Cite

Research Paper

Identification of the mitochondrial protein ADCK2 as a therapeutic oncotarget of NSCLC

Jin-zhi Zhang1*, Jia Liu2*, Yi-xin Xu3*, Wang-yang Pu4*, Ming-jing Shen1, Kan-qiu Jiang1, Yi-ling Yang5, Jingjing Lu5✉, Zhengbo Deng3✉, Yi Yang6✉, Wei-hua Xu1✉

1. Department of Thoracic Surgery, the Second Affiliated Hospital of Soochow University, Suzhou, China.
2. Department of Operation Room, the Second Affiliated Hospital of Soochow University, Suzhou, China.
3. Changshu Hospital affiliated to Nanjing University of Chinese Medicine, Changshu, China.
4. Department of Oncology, the Second Affiliated Hospital of Soochow University, Suzhou, China.
5. Department of Radiotherapy and Oncology, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, China.
6. Department of Nuclear Medicine, the Affiliated Suzhou Science & Technology Town Hospital of Nanjing Medical University, Suzhou, China.
* Co-first authors.

Citation:
Zhang Jz, Liu J, Xu Yx, Pu Wy, Shen Mj, Jiang Kq, Yang Yl, Lu J, Deng Z, Yang Y, Xu Wh. Identification of the mitochondrial protein ADCK2 as a therapeutic oncotarget of NSCLC. Int J Biol Sci 2022; 18(16):6163-6175. doi:10.7150/ijbs.78354. https://www.ijbs.com/v18p6163.htm
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Abstract

Graphic abstract

The aarF domain containing kinase 2 (ADCK2) is a mitochondria-locating protein, important for fatty acid metabolism and coenzyme Q biosynthesis. The bioinformatics results show that elevated ADCK2 transcripts in NSCLC correlate with poor overall survival and poor anti-PD-1/PD-L1 therapy response. ADCK2 is overexpressed in local human NSCLC tissues and various primary and established NSCLC cells. In NSCLC cells, ADCK2 shRNA or CRISPR/Cas9 knockout remarkably suppressed cell viability, proliferation, cell cycle progression, cell mobility, and provoked cell apoptosis. Moreover, ADCK2 depletion disrupted mitochondrial functions in NSCLC cells, causing cytochrome C release, mitochondrial depolarization, DNA damage and ATP reduction. Contrarily, ectopic ADCK2 overexpression promoted NSCLC cell growth. Further studies revealed that ADCK2 depletion inactivated Akt-mTOR signaling in primary NSCLC cells. NSCLC xenograft growth in nude mice was significantly hindered after ADCK2 silencing or knockout. ADCK2 depletion, apoptosis induction and oxidative injury as well as ATP reduction and Akt-mTOR inactivation were detected in ADCK2-silenced or ADCK2-knockout NSCLC xenograft tissues. Together overexpressed ADCK2 is important for the growth of NSCLC cells, representing an important therapeutic molecular oncotarget.

Keywords: NSCLC, ADCK2, mitochondrial function, therapeutic target, cancer growth


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APA
Zhang, J.z., Liu, J., Xu, Y.x., Pu, W.y., Shen, M.j., Jiang, K.q., Yang, Y.l., Lu, J., Deng, Z., Yang, Y., Xu, W.h. (2022). Identification of the mitochondrial protein ADCK2 as a therapeutic oncotarget of NSCLC. International Journal of Biological Sciences, 18(16), 6163-6175. https://doi.org/10.7150/ijbs.78354.

ACS
Zhang, J.z.; Liu, J.; Xu, Y.x.; Pu, W.y.; Shen, M.j.; Jiang, K.q.; Yang, Y.l.; Lu, J.; Deng, Z.; Yang, Y.; Xu, W.h. Identification of the mitochondrial protein ADCK2 as a therapeutic oncotarget of NSCLC. Int. J. Biol. Sci. 2022, 18 (16), 6163-6175. DOI: 10.7150/ijbs.78354.

NLM
Zhang Jz, Liu J, Xu Yx, Pu Wy, Shen Mj, Jiang Kq, Yang Yl, Lu J, Deng Z, Yang Y, Xu Wh. Identification of the mitochondrial protein ADCK2 as a therapeutic oncotarget of NSCLC. Int J Biol Sci 2022; 18(16):6163-6175. doi:10.7150/ijbs.78354. https://www.ijbs.com/v18p6163.htm

CSE
Zhang Jz, Liu J, Xu Yx, Pu Wy, Shen Mj, Jiang Kq, Yang Yl, Lu J, Deng Z, Yang Y, Xu Wh. 2022. Identification of the mitochondrial protein ADCK2 as a therapeutic oncotarget of NSCLC. Int J Biol Sci. 18(16):6163-6175.

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