FosL1 Regulates Regional Metastasis of Head and Neck Squamous Cell Carcinoma by Promoting Cell Migration, Invasion, and Proliferation

Abstract

Background/Aim: We evaluated the impact of FosL1, a member of the activated protein-1 family, on the pathways leading to regional metastasis of head and neck squamous cell carcinoma (HNSCC). Materials and Methods: We examined the influence of small interfering RNA (siRNA) and short heparin RNA (shRNA) mediated knockdown of FosL1 on cell migration, invasion, and proliferation in vitro as well as on regional metastasis in vivo. The prognostic significance of FosL1 was also analyzed using the Kaplan-Meier plotter using data from an HNSCC patient database. Results: Down-regulation of FosL1 inhibited cell migration, invasion, and proliferation in vitro, decreased the incidence of regional metastases, and prolonged the survival of mice in vivo. We also determined that HNSCC patients with higher expression levels of FosL1 had a significantly shorter survival time than those with low expression of FosL1. Conclusion: FosL1 plays a crucial role in promoting cell migration, invasion, and proliferation in HNSCC.Head and neck squamous cell carcinoma (HNSCC) patients often have advanced disease with cervical lymph node metastases at the time of diagnosis (1), resulting in poor prognosis despite advances in treatment modalities. Furthermore, treatment failure is often associated with locoregional recurrence in HNSCC patients. The presence of cervical lymph node metastasis is reported as one of the reliable prognostic factors for the survival of patients with HNSCC (2). Therefore, it is necessary to elucidate the mechanisms of cervical lymph node metastases to develop new treatments to improve the survival outcomes of patients with HNSCC.We previously reported that JunB, a member of the AP-1 family, regulates metastatic pathways by promoting cell invasion and migration of HNSCC (3). Thus, AP-1, which forms heterodimers with proteins of the Fos family, the Jun family, musculoaponeurotic fibrosarcoma (Maf), and activating transcription factor (ATF) (4, 5), plays crucial roles in regulating cellular processes such as proliferation, differentiation, death, and survival induced by growth factors, cell-matrix interactions, infections, cytokines, and stresses (6, 7). The Fos family of proteins and c-Jun have also been reported to induce tumorigenesis and metastasis (3,4,(8)(9)(10).These studies led us to characterize the regional metastatic potential in vivo using 14 different HNSCC cell lines in an orthotopic nude mouse model. We performed an upstream and key node analysis using whole-gene microarray data of these lines to determine key molecules associated with the regional metastatic potential of HNSCC. As we identified FosL1 as one of the key molecules associated with the regional metastatic potential of HNSCC, we examined the impact of FosL1 knockdown on cell migration in vitro, as well as cervical lymph node metastasis in vivo, to test the hypothesis that FosL1 could be the key molecule regulating the pathways associated with neck lymph node metastasis in HNSCC.

Platelet membrane‐derived microparticles may be biomarkers in patients with hepatocellular carcinoma and can promote the invasion and metastasis of hepatoma carcinoma cells

“…Through transcriptional sequencing analysis, we found that the gene expression of FOSL1 and RAB5B was significantly increased after PMPs were added to two HCC cell lines. FosL1 plays a crucial role in promoting cell migration, invasion, and proliferation in neck squamous cell carcinoma, 39 and knockdown of RAB5B also inhibits cell proliferation, migration, and invasion in human breast cancer stem cell-like cells. 40 Under the intervention of PMPs, the changes of relevant proliferation genes also confirmed the fact that the tumor volume increased in vivo.…”

MiR-33a targets FOSL1 and EN2 as a clinical prognostic marker for sarcopenia by glioma

“…FOS1 also has prognostic value in various epithelial tumors, and its overexpression is associated with tumor aggressiveness, chemotherapy resistance, tumor progression, and poor survival prognosis ( Yu et al, 2013 ; Gao et al, 2017 ; Vallejo et al, 2017 ; Xu et al, 2017 ; Sobolev et al, 2022 ). It has been shown that FOSL1 can promote the development and invasion of colorectal cancer through the Smurf1-mediated FBXL2/Wnt/β-catenin axis and the migration, invasion, and proliferation of breast, head, and neck squamous cell carcinoma, pancreatic cancer, bladder cancer, and prostate cancer ( Elangovan et al, 2018 ; Luo et al, 2018 ; Cui et al, 2020 ; Dai et al, 2021 ; Hyakusoku et al, 2021 ; Liu et al, 2021 ). In addition, FOSL1 also mediates the dephosphorylation of proliferation and apoptosis bridging protein 15 (PEA15) by upregulating dual-specificity phosphatase 7 (DUSP7), which increases drug resistance in breast cancer ( Li et al, 2022b ).…”

FOS-Like Antigen 1 Expression Was Associated With Survival of Hepatocellular Carcinoma Patients

“…FOS-like antigen 1 (FOSL1) has an important prognostic value in different tumors, as its overexpression correlates with tumors progression or worse patient survival [ 10 ]. Furthermore, the functions of FOSL1 in promoting epithelial-mesenchymal transition, resulting in cancer spread and metastasis, were reported in various malignant tumors, such as breast, colorectal, prostatic, lung, nasopharyngeal, thyroid, pancreatic, gastric carcinomas, and malignant melanoma [ 11 ].…”