ABSTRACT Colon cancer is the most aggressive tumor in both men and women globally. As many the chemotherapeutic regimens have adverse side effects and contribute to the resistance and

recurrence, therefore, finding novel therapeutic targets and developing effective agents are urgent. Based on the TCGA and GTEx database analysis, RSK1 and MSK2 were found abnormal expressed

in colon cancer. RSK1 and MSK2 were overexpressed in colon cancer tissues confirmed by western blot and IHC. After knocking down RSK1 or MSK2, cell proliferation and anchorage-independent

cell growth were markedly inhibited. Using a computer docking model, we identified a novel dual-target inhibitor, APIO-EE-07, that could block both RSK1 and MSK2 kinase activity in a

SCID mice. In summary, our results demonstrate that RSK1 and MSK2 are the potential targets for the treatment of colon cancer. APIO-EE-07, a novel dual-target inhibitor of RSK1 and MSK2, can

suppress the growth of colon cancer by attenuating RSK1 and MSK2 signaling. Access through your institution Buy or subscribe This is a preview of subscription content, access via your

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SUPPRESS COLORECTAL CANCER GROWTH Article Open access 09 March 2022 ALBENDAZOLE INHIBITS COLON CANCER PROGRESSION AND THERAPY RESISTANCE BY TARGETING UBIQUITIN LIGASE RNF20 Article 26

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Scholar  Download references FUNDING This work was supported by the Key Science and Technology Program of Henan Province, China (182102310125) and the Key program of TCM research in Henan

Province, China (2018ZY1016, 2019ZY1037). AUTHOR INFORMATION Author notes * These authors have contributed equally: Guoguo Jin, Mingyang Yan, Kangdong Liu AUTHORS AND AFFILIATIONS * The

Henan Luoyang Orthopedic Hospital, Zhengzhou, Henan, People’s Republic of China Guoguo Jin & Zhiping Guo * China-US (Henan) Hormel Cancer Institute, Zhengzhou, People’s Republic of China

Guoguo Jin, Mingyang Yan, Kangdong Liu, Dhilli Rao Gorja, Kyle Vaughn Laster & Zigang Dong * Henan Provincial Cooperative Innovation Center of Cancer Chemoprevention, Zhengzhou

University, Zhengzhou, Henan, People’s Republic of China Guoguo Jin & Kangdong Liu * Pathophysiology Department, School of Basic Medical Science, College of Medicine Zhengzhou

University, Zhengzhou, Henan, People’s Republic of China Kangdong Liu & Zigang Dong * The Hormel Institute, University of Minnesota, Austin, MN, USA Ke Yao, Hanyong Chen & Kanamata

Reddy * Center of Bio Repository, Affiliated Tumor Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China Chengjuan Zhang * Department of Pathology and

Pathophysiology, School of Basic Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, Henan, People’s Republic of China Yang Yi Authors * Guoguo Jin View author publications

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author inPubMed Google Scholar CONTRIBUTIONS GJ, KY, ZG, and ZD designed this study. GJ, MY, and KL performed the experiment, analyzed data, and prepared figures. KD and DG synthesis

chemicals. HC contributed to computational analysis. KL analyzed of GEPIA database. ZJ and YY performed some explements. GJ wrote paper and ZD revised the paper. CORRESPONDING AUTHORS

Correspondence to Zhiping Guo or Zigang Dong. ETHICS DECLARATIONS CONFLICT OF INTEREST The authors declare that they have no conflict of interest. ADDITIONAL INFORMATION PUBLISHER’S NOTE

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G., Yan, M., Liu, K. _et al._ Discovery of a novel dual-target inhibitor against RSK1 and MSK2 to suppress growth of human colon cancer. _Oncogene_ 39, 6733–6746 (2020).

https://doi.org/10.1038/s41388-020-01467-w Download citation * Received: 26 April 2020 * Revised: 11 August 2020 * Accepted: 10 September 2020 * Published: 22 September 2020 * Issue Date: 22

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