In HPV-Positive HNSCC Cells, Functional Restoration of the P53/p21 Pathway by Proteasome Inhibitor Bortezomib Does Not Affect Radio- or Chemosensitivity

Overview

Journal Transl Oncol

Specialty Oncology

Date 2018 Dec 17

PMID 30554133

Citations 8

Authors

Steve Seltzsam

Frank Ziemann

Kristin Dreffke

Stefanie Preising

Andrea Arenz

Ulrike Schotz

Rita Engenhart-Cabillic

Ekkehard Dikomey

Andrea Wittig

Affiliations

Soon will be listed here.

Abstract

Human papillomavirus (HPV) associated squamous cell carcinomas of the head and neck region (HPV+ HNSCCs) harbor diverging biological features as compared to classical noxa-induced (HPV-) HNSCC. One striking difference between subtypes is that the tumor suppressor gene TP53 is usually not mutated in HPV+ HNSCCs. However, p53 is inhibited by viral oncoprotein E6, leading to premature proteasomal degradation. We asked whether bortezomib (BZM), a clinically approved inhibitor of the proteasome, can functionally restore p53 and investigated in how far this will result in an enhanced radio- or chemosensitivity of HPV+ HNSCC cell lines. For all four HPV+ cell lines tested, BZM led to functional restoration of p53 and transactivation of downstream protein p21. In HPV+ cells, BZM also restored the radiation-induced p53/p21 transactivation. Consistently, in HPV+ cells, a restored G1 arrest as well as enhanced apoptosis were seen when BZM was given prior to irradiation (IR) or cisplatin (CDDP). BZM alone reduced the clonogenic survival of both HPV- and HPV+ cells. However, if BZM was combined with IR or CDDP, BZM did not significantly enhance radio- or chemosensitivity of HPV+ or HPV- HNSCC cell lines.

Citing Articles

Novel Predictive Biomarkers in the Head and Neck Squamous Cell Carcinoma (HNSCC).

Miniuk M, Reszec-Gielazyn J, Bortnik P, Borsukiewicz A, Mroczek A J Clin Med. 2024; 13(19).

PMID: 39407936 PMC: 11477133. DOI: 10.3390/jcm13195876.

p53 Modulates Radiosensitivity in Head and Neck Cancers-From Classic to Future Horizons.

Mirestean C, Iancu R, Iancu D Diagnostics (Basel). 2022; 12(12).

PMID: 36553058 PMC: 9777383. DOI: 10.3390/diagnostics12123052.

IL1 Pathway in HPV-Negative HNSCC Cells Is an Indicator of Radioresistance After Photon and Carbon Ion Irradiation Without Functional Involvement.

Tiwari D, Hannen R, Unger K, Kohl S, Hess J, Lauber K Front Oncol. 2022; 12:878675.

PMID: 35530351 PMC: 9072779. DOI: 10.3389/fonc.2022.878675.

Restoring p53 Function in Head and Neck Squamous Cell Carcinoma to Improve Treatments.

de Bakker T, Journe F, Descamps G, Saussez S, Dragan T, Ghanem G Front Oncol. 2022; 11:799993.

PMID: 35071005 PMC: 8770810. DOI: 10.3389/fonc.2021.799993.

HPV E7 inhibits cell pyroptosis by promoting TRIM21-mediated degradation and ubiquitination of the IFI16 inflammasome.

Song Y, Wu X, Xu Y, Zhu J, Li J, Zou Z Int J Biol Sci. 2020; 16(15):2924-2937.

PMID: 33061806 PMC: 7545706. DOI: 10.7150/ijbs.50074.

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