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Hao T, Gan YH. ΔNp63α promotes the expression and nuclear translocation of PTEN, leading to cisplatin resistance in oral cancer cells. Am J Transl Res. 2020;12(10):6187-6203
Hao, T., & Gan, Y. H. (2020). ΔNp63α promotes the expression and nuclear translocation of PTEN, leading to cisplatin resistance in oral cancer cells. American journal of translational research, 12(10), 6187-6203.
Hao, Ting, and Gan, Ye-Hua. "ΔNp63α promotes the expression and nuclear translocation of PTEN, leading to cisplatin resistance in oral cancer cells." American journal of translational research vol. 12,10 (2020): 6187-6203.
Hao T, Gan YH. ΔNp63α promotes the expression and nuclear translocation of PTEN, leading to cisplatin resistance in oral cancer cells. Am J Transl Res. 2020 Oct 15;12(10):6187-6203. eCollection 2020. PMID: 33194023; PMCID: PMC7653557.
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Am J Transl Res. 2020 Oct 15;12(10):6187-6203. eCollection 2020.

ΔNp63α promotes the expression and nuclear translocation of PTEN, leading to cisplatin resistance in oral cancer cells.

American journal of translational research

Ting Hao, Ye-Hua Gan

Affiliations

  1. Central Laboratory, Peking University School and Hospital of Stomatology 22 Zhongguancun Avenue South, Haidian District, Beijing 100081, China.
  2. Department of Oral & Maxillofacial, Peking University School and Hospital of Stomatology 22 Zhongguancun Avenue South, Haidian District, Beijing 100081, China.

PMID: 33194023 PMCID: PMC7653557

Abstract

Pan-histone deacetylase (HDAC) inhibitors can induce the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) protein. However, the underlying mechanism by which this occurs remains unclear. In this study, we show that pan-HDAC inhibitors, including trichostatin A, suberoylanilide hydroxamic acid, and sodium butyrate, were able to induce PTEN mRNA and protein expression via the acetylation of the transcription factor ΔNp63α by inhibiting HDAC1 and HDAC3. ΔNp63α enhanced PTEN promoter activity by binding two newly identified recognition sites on it. Unfortunately, the inhibition of HDAC1 or HDAC3 failed to activate PTEN, as knockdown of HDAC1 inhibited both membrane-bound and nuclear PTEN, and knockdown of HDAC3 only induced cytoplasmic PTEN. Furthermore, the overexpression of ΔNp63α downregulated membrane-bound PTEN but enhanced the nuclear translocation of PTEN, leading to the cisplatin resistance of oral cancer cells. PTEN accumulated in the nuclei of cancerous cells and normal cells when ΔNp63α was highly expressed in specimens from patients with squamous cell carcinoma of the tongue. However, inhibiting either HDAC1 or HDAC6 prevented the nuclear translocation of PTEN and attenuated cisplatin resistance. These results suggest that chemotherapeutic inhibitors of HDAC1 or HDAC6, together with cisplatin, might improve outcomes for patients with squamous cell carcinoma of the tongue.

AJTR Copyright © 2020.

Keywords: PTEN; cisplatin resistance; ΔNp63α

Conflict of interest statement

None.

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