ACSS2/AMPK/PCNA pathway‑driven proliferation and chemoresistance of esophageal squamous carcinoma cells under nutrient stress

  • Authors:
    • Lei Mi
    • Yuepeng Zhou
    • Dan Wu
    • Qing Tao
    • Xuefeng Wang
    • Haitao Zhu
    • Xingyu Gao
    • Jingzhi Wang
    • Rui Ling
    • Jing Deng
    • Chaoming Mao
    • Deyu Chen
  • View Affiliations

  • Published online on: October 9, 2019     https://doi.org/10.3892/mmr.2019.10735
  • Pages: 5286-5296
  • Copyright: © Mi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Although platinum‑based chemotherapy is the first‑line choice for locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) patients, accelerated recurrence and chemoresistance remain inevitable. New evidence suggests that metabolism reprogramming under stress involves independent processes that are executed with a variety of proteins. This study investigated the functions of nutrient stress (NS)‑mediated acetyl‑CoA synthetase short‑chain family member 2 (ACSS2) in cell proliferation and cisplatin‑resistance and examined its combined effects with proliferating cell nuclear antigen (PCNA), a key regulator of DNA replication and repair. Here, it was demonstrated that under NS, when the AMP‑activated protein kinase (AMPK) pathway was activated, ESCC cells maintained proliferation and chemoresistance was distinctly upregulated as determined by CCK‑8 assay. As determined using immunoblotting and RT‑qPCR, compared with normal esophageal epithelial cells (Het‑1A), ESCC cells were less sensitive to NS and showed increased intracellular levels of ACSS2. Moreover, it was shown that ACSS2 inhibition by siRNA not only greatly interfered with proliferation under NS but also participated in DNA repair after cisplatin treatment via PCNA suppression, and the acceleration of cell death was dependent on the activation of the AMPK pathway as revealed by the Annexin V/PI and TUNEL assay results. Our study identified crosstalk between nutrient supply and chemoresistance that could be exploited therapeutically to target AMPK signaling, and the results suggest ACSS2 as a potential biomarker for identifying higher‑risk patients.
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December-2019
Volume 20 Issue 6

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Mi L, Zhou Y, Wu D, Tao Q, Wang X, Zhu H, Gao X, Wang J, Ling R, Deng J, Deng J, et al: ACSS2/AMPK/PCNA pathway‑driven proliferation and chemoresistance of esophageal squamous carcinoma cells under nutrient stress. Mol Med Rep 20: 5286-5296, 2019
APA
Mi, L., Zhou, Y., Wu, D., Tao, Q., Wang, X., Zhu, H. ... Chen, D. (2019). ACSS2/AMPK/PCNA pathway‑driven proliferation and chemoresistance of esophageal squamous carcinoma cells under nutrient stress. Molecular Medicine Reports, 20, 5286-5296. https://doi.org/10.3892/mmr.2019.10735
MLA
Mi, L., Zhou, Y., Wu, D., Tao, Q., Wang, X., Zhu, H., Gao, X., Wang, J., Ling, R., Deng, J., Mao, C., Chen, D."ACSS2/AMPK/PCNA pathway‑driven proliferation and chemoresistance of esophageal squamous carcinoma cells under nutrient stress". Molecular Medicine Reports 20.6 (2019): 5286-5296.
Chicago
Mi, L., Zhou, Y., Wu, D., Tao, Q., Wang, X., Zhu, H., Gao, X., Wang, J., Ling, R., Deng, J., Mao, C., Chen, D."ACSS2/AMPK/PCNA pathway‑driven proliferation and chemoresistance of esophageal squamous carcinoma cells under nutrient stress". Molecular Medicine Reports 20, no. 6 (2019): 5286-5296. https://doi.org/10.3892/mmr.2019.10735