HSP60‑knockdown suppresses proliferation in colorectal cancer cells via activating the adenine/AMPK/mTOR signaling pathway

Guo,Jianying; Zhu,Songbiao; Deng,Haiteng; Xu,Renhua

doi:10.3892/ol.2021.12891

HSP60‑knockdown suppresses proliferation in colorectal cancer cells via activating the adenine/AMPK/mTOR signaling pathway

Authors:
- Jianying Guo
- Songbiao Zhu
- Haiteng Deng
- Renhua Xu
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Affiliations: School of Nursing, Binzhou Medical University, Yantai, Shandong 264003, P.R. China, Key Laboratory of Bioinformatics, Ministry of Education, Center for Synthetic and Systematic Biology, School of Life Sciences, Tsinghua University, Beijing 100084, P.R. China
Published online on: July 1, 2021 https://doi.org/10.3892/ol.2021.12891
Article Number: 630
Copyright: © Guo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Colorectal cancer (CRC) is the fourth most lethal cancer in the world. Heat shock protein 60 (HSP60), a mitochondrial chaperone that maintains mitochondrial proteostasis, is highly expressed in tumors compared with in paracancerous tissues, suggesting that high HSP60 expression benefits tumor growth. To determine the effects of HSP60 expression on tumor progression, stable HSP60‑knockdown HCT116 cells were constructed in the present study, revealing that knockdown of HSP60 inhibited cell proliferation. Proteomic analysis demonstrated that mitochondrial proteins were downregulated, indicating that knockdown of HSP60 disrupted mitochondrial homeostasis. Metabolomic analysis demonstrated that cellular adenine levels were >30‑fold higher in HSP60‑knockdown cells than in control cells. It was further confirmed that elevated adenine activated the AMPK signaling pathway, which inhibited mTOR‑regulated protein synthesis to slow down cell proliferation. Overall, the current results provide a valuable resource for understanding mitochondrial function in CRC, suggesting that HSP60 may be a potential target for CRC intervention.

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