HSP90AB1 Promotes the Proliferation, Migration, and Glycolysis of Head and Neck Squamous Cell Carcinoma

Abstract

Background: Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer worldwide. Heat shock protein 90 alpha family class B member 1 (HSP90AB1) is highly expressed in a variety of cancers and is associated with poor prognosis, however, its role in HNSCC is still poorly understood. This study aimed to explore the function HSP90AB1 played in HNSCC progression. Methods: The expression level of HSP90AB1 in HNSCC was analyzed by bioinformatics analysis and western blotting, and its relationship with clinicopathological parameters was analyzed by bioinformatics analysis and immunohistochemistry. Three stable HSP90AB1 knockdown HNSCC cell lines were constructed by lentiviral transfection. The effect of HSP90AB1 knockdown on the proliferation and migration of HNSCC cells was tested by CCK-8 assay, EdU incorporation assay, colony formation assay, nude mouse xenograft models, transwell migration assay, wound healing assay, and western blotting. The effect of HSP90AB1 knockdown on glycolysis in HNSCC cells was assessed by quantitative real-time PCR and related assay kits. Finally, the levels of Akt and phospho-Akt (Ser473) proteins after HSP90AB1 knockdown were detected by western blotting. Results: HSP90AB1 was highly expressed in HNSCC and associated with T grade, lymph node metastasis, and prognosis. Knockdown of HSP90AB1 inhibited the proliferation, migration, and glycolysis of HNSCC, and reduced the level of phospho-Akt. Conclusion: HSP90AB1 functions as an oncogene in HNSCC, and has the potential to become a prognostic factor and therapeutic target.

Large-scale identification of lysine crotonylation reveals its potential role in oral squamous cell carcinoma

“…Notably, the crotonylation level of HSP90AB1, a vital upstream regulator of glycolysis, was up-regulated by up to 9-fold change at K265 site [21]. Therefore, we speculated that the crotonylation level of HSP90AB1 would in uence its glycolysis regulation function, and the preliminary experimental results also con rmed this.…”

“…Knockdown of HSP90AB1 in CAL27 cells was conducted using a lentiviral vector (Genechem, Shanghai, China) carrying a short-hairpin RNA (shRNA) speci c for HSP90AB1, according to the manufacturer's instructions. The sequence of the HSP90AB1 shRNA and the transfection operations can be found in our previous reports [21].…”

“…The detection of pyruvate, ATP and lactic acid were carried out as we reported before [21]. Pyruvate assay kit (A081-1-1), ATP assay kit (A095-2-1) and Lactic Acid assay kit (A019-2-1) were used (Nanjing Jiancheng Bioengineering Institute, Nanjing, China).…”

“…In our previous studies, we found that HSP90AB1 was involved in regulating glycolysis in OSCC [21]. To investigate whether crotonylation affects HSP90AB1's ability to regulate glycolysis, we constructed both HSP90AB1 mutant and wild-type plasmids.…”

Fisetin, a dietary flavonoid, increases the sensitivity of chemoresistant head and neck carcinoma cells to cisplatin possibly through HSP90AA1/IL‐17 pathway

“…To date, there are no specific inhibitors that specifically target HSP90AA1. This is because inhibitors found at this stage may simultaneously inhibit multiple members of the HSP90 family or/and other molecules, making it difficult to reflect their specific inhibition against HSP90AA1 (H. Zhang, Yin, et al, 2022). For this reason, in order to avoid confusion about the results caused by the non‐specific nature of the inhibitors, RNA interference was still the main research tool in recent studies on HSP90AA1 (C. Liu et al, 2022; H. Zhang, Yin, et al, 2022).…”