Oncogenic E6 and/or E7 proteins drive proliferation and invasion of human papilloma virus‑positive head and neck squamous cell cancer through upregulation of Ror2 expression

Avincsal,Mehmet Ozgur; Kamizaki,Koki; Jimbo,Naoe; Shinomiya,Hirotaka; Nibu,Ken-Ichi; Nishita,Michiru; Minami,Yasuhiro

doi:10.3892/or.2021.8099

Oncogenic E6 and/or E7 proteins drive proliferation and invasion of human papilloma virus‑positive head and neck squamous cell cancer through upregulation of Ror2 expression

Authors:
- Mehmet Ozgur Avincsal
- Koki Kamizaki
- Naoe Jimbo
- Hirotaka Shinomiya
- Ken-Ichi Nibu
- Michiru Nishita
- Yasuhiro Minami
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Affiliations: Division of Cell Physiology, Department of Physiology and Cell Biology, Graduate School of Medicine, Kobe University, Kobe, Hyogo 650‑0017, Japan, Department of Diagnostic Pathology, Graduate School of Medicine, Kobe University, Kobe, Hyogo 650‑0017, Japan, Department of Otolaryngology‑Head and Neck Surgery, Graduate School of Medicine, Kobe University, Kobe, Hyogo 650‑0017, Japan
Published online on: May 31, 2021 https://doi.org/10.3892/or.2021.8099
Article Number: 148

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Abstract

Ror2 (receptor tyrosine kinase like orphan receptor 2) is highly expressed in various types of cancers; in the majority of these cancers, Ror2 expression is associated with more aggressive disease states. Recently, it has been reported that Ror2 is highly expressed in human papilloma virus (HPV)‑positive head and neck squamous cell cancer (HNSCC) cell lines, presumably indicating that Ror2 plays a critical role in HPV‑related cancers. However, the function of Ror2 in HPV‑positive HNSCC is currently unknown. Here, we first examined the expression levels of Ror2 in clinical specimens from patients with HPV‑negative and HPV‑positive oropharyngeal squamous cell cancer (OPSCC) via immunohistochemical analysis. We found that Ror2 was expressed in both HPV‑negative and HPV‑positive OPSCC tissues. We then confirmed that HPV‑positive HNSCC cell line, UPCI:SCC152 cells, express Ror2 higher than HPV‑negative cell lines as previously reported. Suppressed expression of HPV E6/7 resulted in reduced expression levels of Ror2. We also revealed that Ror2 downregulation significantly inhibited the proliferation of UPCI:SCC152 cells without inducing apoptosis. Moreover, Ror2 knockdown decelerated G₁/S phase progression and abrogated invasive migration of UPCI:SCC152 cells. These results provide strong evidence that E6 and/or E7 oncoproteins regulate the progression of HPV‑positive HNSCC by upregulating Ror2 expression, suggesting that Ror2 could potentially be a novel target in HPV‑related cancers.

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