Caveolin‐1 promotes cancer progression via inhibiting ferroptosis in head and neck squamous cell carcinoma

Abstract

Background: Head and neck squamous cell carcinoma (HNSCC) is an aggressive disease worldwide. Much progress has been made in exploring mechanisms and improving the therapy of HNSCC, but only a few studies have focused on the role of ferroptosis on HNSCC progression. The current study aimed to reveal the underlining mechanisms that caveolin-1 (CAV1)-ROS (reactive oxygen species)-ferroptosis axis affect the process of HNSCC and discover novo therapeutic targets or strategies. Methods:The role of CAV1 in ferroptosis was analyzed by FerrDb, and its clinical significance was examined by TCGA dataset of HNSCC. The expressions of caveolin-1 (CAV1) in HNSCC tissues were measured by immunohistochemistry, western blot, and real-time PCR assay. Three siRNA sequences were designed to silence CAV1 mRNA in HNSCC cells. Cell proliferation, colony formation, wound-healing, and transwell assays were used to examine the proliferation, migration, and invasion of cancer cells.ROS evaluation and intracellular Fe 2+ content assays were performed to examine the levels of ferroptosis.Results: Through the analysis with published data, CAV1 was found to overexpress in HNSCC than normal tissues, and was one of the vital suppressors of ferroptosis pathway. Our study showed that CAV1 was over expressed in HNSCC tissues and the high level of CAV1 predicted poorer prognosis. Further experiments indicated that CAV1 could inhibit the ferroptosis of cancer cells and promote the proliferation, migration and invasion.Conclusions: Overexpression of CAV1 in HNSCC inhibited the process of ferroptosis, leading to aggressive phenotypes, as well as worse prognosis. The regulatory pathway of CAV1 and ferroptosis are potential targets for designing diagnostic and combined therapeutic strategies for HNSCC patients.

Identification and validation of a ferroptosis-related prognostic risk-scoring model and key genes in small cell lung cancer

“…Ferroptosis has been reported to modulate the TME to inhibit tumor progression and improve prognosis (19,20). Our study first developed a novel risk-scoring model based on 5 ferroptosis-related prognostic genes from SCLC data from the cBioPortal dataset.…”

“…Recent evidence suggests that activation of ferroptosis can overcome tumor development and reduce the sensitivity of the tumor to chemotherapy ( 8 ). Ferroptosis has been reported to modulate the TME to inhibit tumor progression and improve prognosis ( 19 , 20 ). Our study first developed a novel risk-scoring model based on 5 ferroptosis-related prognostic genes from SCLC data from the cBioPortal dataset.…”

Epithelial Membrane Protein 1 Promotes Sensitivity to RSL3-Induced Ferroptosis and Intensifies Gefitinib Resistance in Head and Neck Cancer

“…Recently, sequence-based studies have shown that ferroptosis-related gene signature plays an important role in the development and treatment of HNSCC [ 18 – 20 ]. CAV1, which could inhibit ferroptosis, leads to cancer progression in HSNCC [ 21 ]. Li et al reveal that IL-6 induces ferroptosis resistance by protecting tumor cells from ROS and promoting HNSCC progression [ 22 ].…”

Characterization of the Ferroptosis-Related Genes for Prognosis and Immune Infiltration in Low-Grade Glioma

“…It is characterized by dysbalance in the regulation of intracellular iron metabolism and membrane lipid peroxidation ( Ursini and Maiorino, 2020 ). The function of ferroptosis in several types of cancer has been reported previously, including breast cancer ( Li H. et al, 2022 ), hepatocellular carcinoma ( Chen et al, 2022 ), gastric cancer ( Zhang et al, 2021 ), head neck squamous cell carcinoma ( Lu et al, 2021 ), lung cancer ( Li and Liu, 2022 ), renal cell carcinoma ( Du et al, 2021 ), ovarian cancer ( Li H.-W. et al, 2022 ), and pancreatic cancer ( Liu et al, 2021 ). Mou et al (2022 ) has found that for LGG the SAT1 activation is closely related to ferroptosis upon ROS induction.…”