P4HA2 contributes to head and neck squamous cell carcinoma progression and EMT through PI3K/AKT signaling pathway

Sep 21, 2026

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Head and neck squamous cell carcinoma (HNSCC) is a lethal disease with poor outcomes in advanced stages, motivating investigation of P4HA2 expression and biological impact, as well as the underlying mechanisms. Integrated bioinformatics analyses assessed P4HA2 expression patterns, prognostic significance, and likely functions. In vitro experiments on CAL-27 cells evaluated proliferation, migration, invasion, apoptosis, and EMT markers, while western blotting examined PI3K/AKT signaling. Results showed elevated P4HA2 in HNSCC, linking overexpression to aggressiveness and worse prognosis, and demonstrating PI3K/AKT involvement.

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CategoryHealthcare

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Medical Oncology (2024) 41:163 [https://doi.org/10.1007/s12032-024-02358-w](https://doi.org/10.1007/s12032-024-02358-w) P4HA2 contributes to head and neck squamous cell carcinoma progression and EMT through PI3K/AKT signaling pathway Yan‑Ling Wu1 · Wan Liu2 · Tingting Zhao2 · Jing Jin1 Received: 23 January 2024 / Accepted: 14 March 2024 / Published online: 23 May 2024 © The Author(s) 2024 Abstract Head and neck squamous cell carcinoma (HNSCC) can be defined as a deadly illness with a dismal prognosis in advanced stages. Therefore, we seek to examine P4HA2 expression and effect in HNSCC, along with the underlying mechanisms. This study utilized integrated bioinformatics analyses to evaluate the P4HA2 expression pattern, prognostic implication, and probable function in HNSCC. The study conducted various in vitro experiments, including colony formation, CCK-8, flow cytometry, wound healing, and transwell assays, on the human HNSCC cell line CAL-27 to examine the involvement of P4HA2 in HNSCC progression. Moreover, western blotting was used to investigate epithelial-mesenchymal transition (EMT) markers and PI3K/AKT pathway markers to elucidate the underlying mechanisms. P4HA2 expression was significantly enhanced in HNSCC, and its overexpression was correlated to tumor aggressiveness and a poor prognosis in patients. Based on in vitro experiments, the overexpressed P4HA2 enhanced cell proliferation, migration, invasion, as well as EMT while reducing apoptosis, whereas P4HA2 silencing exhibited the reverse effect. P4HA2 overexpression enhanced PI3K/ AKT phosphorylation in HNSCC cells. Moreover, LY294002 was observed to counteract the effects of upregulated P4HA2 on proliferation, migration, invasion, and EMT in HNSCC. Collectively, we indicated that P4HA2 promoted HNSCC progression and EMT via PI3K/AKT signaling pathway. Keywords P4HA2 · Head and neck squamous cell carcinoma · EMT · PI3K/AKT pathway · Prognostic marker Yan-Ling Wu and Wan Liu have contributed equally to this work. * Jing Jin [jinjing@cicams.ac.cn](jinjing@cicams.ac.cn) [Yan-Ling Wu](Yan-Ling Wu) [wuyl_1202@163.com](wuyl_1202@163.com) Wan Liu [tyr1573@163.com](tyr1573@163.com) Tingting Zhao [zttdistinctive06@163.com](zttdistinctive06@163.com) 1 Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/ Cancer Hospital and Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, Guangdong, China 2 Department of Head and Neck Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, Guangdong, China Introduction Head and neck cancers, which encompass various cancers such as nasopharyngeal cancer, oral cancer, laryngeal cancer, and hypopharyngeal cancer, can manifest with diverse primary sites and pathological subtypes. Squamous cell carcinoma is the most common type of head and neck cancer, accounting for over 90% of cases [1] . Head and necksquamous cell carcinoma (HNSCC) is considered a widely occurring malignancy on a global scale, with an excess of 800,000 incidences and over 350,000 mortalities annually [2] . HNSCC threats, to a great extent, not only human health but also their quality of life due to its elevated rates of primary-site recurrence and metastasis, as well as latestage diagnosis and poor prognosis [3] . Although surgical technology has improved dramatically, the use of radiation and chemotherapy has demonstrated enhanced management of local HNSCC control; these treatment options can lead to cosmetic deformity and functional impairment of vital functions [4] . The low overall 5-year survival rate that is shown in HNSCC patients can be attributed to the increased treatment failure and recurrence rates, besides the nodal metastasis. Despite treatment, the five-year survival rate of

FAQs

What is the main goal of the study regarding P4HA2 in HNSCC?

To examine P4HA2 expression and its effects in HNSCC, including the underlying mechanisms and its diagnostic/prognostic value.

How did the researchers assess the involvement of P4HA2 in HNSCC progression?

They used integrated bioinformatics plus in vitro assays (colony formation, CCK-8, flow cytometry, wound healing, transwell) on CAL-27 cells, together with western blotting for EMT and PI3K/AKT markers.

What role does P4HA2 play in EMT and cell behavior in HNSCC?

P4HA2 overexpression enhanced proliferation, migration, invasion, and EMT while reducing apoptosis; silencing P4HA2 showed the opposite effects.

Sep 21, 2026

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