scholarly journals Alternatively spliced ANLN isoforms synergistically contribute to the progression of head and neck squamous cell carcinoma

2021 ◽  
Vol 12 (8) ◽  
Author(s):  
Erliang Guo ◽  
Xionghui Mao ◽  
Xueying Wang ◽  
Lunhua Guo ◽  
Changming An ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Cell Lines ◽  
Squamous Cell ◽  
Binding Protein ◽  
Neck Squamous Cell Carcinoma ◽  
Alternatively Spliced

AbstractHead and neck squamous cell carcinoma (HNSCC) is a common cancer with high mortality. Anilin actin-binding protein (ANLN) has been reported to be associated with carcinogenesis in multiple tumors. However, the expression pattern and functional effects of ANLN in HNSCC remain to be unclear. Clinical data and online databases were used to analyze the expression of ANLN and its relationship with HNSCC patient survival. Expression of two major splice variants of ANLN was assessed in HNSCC tissues and cell lines. The functional effects and related mechanisms of ANLN isoforms were investigated in HNSCC in vitro and in vivo. Our study showed that patients with high expression of ANLN had a poor prognosis. The two primary isoforms of ANLN transcripts ANLN-201 and ANLN-210 were highly expressed in HNSCC tissues and cell lines. Knockout of ANLN restrained cell proliferation, migration, and invasion of SCC-9 cells. Mechanically, ANLN-201 could interact with c-Myc to keep its protein stability, thereby playing a oncogenic role in HNSCC. ANLN-210 could be transferred to macrophages via exosomes by binding to RNA-binding protein hnRNPC. Exosomal ANLN-210 promoted macrophage polarization via PTEN/PI3K/Akt signaling pathway, thus stimulating tumor growth of HNSCC. ANLN was an independent prognostic factor in patients with HNSCC. Alternatively spliced ANLN isoforms collaboratively promote HNSCC tumorigenesis in vitro and in vivo, which might provide the in-depth role and mechanism of ANLN in HNSCC development.

scholarly journals Alternatively Spliced ANLN Isoforms Synergistically Contribute To The Progression of Head and Neck Squamous Cell Carcinoma

2021 ◽  
Author(s):  
Erliang Guo ◽  
Xionghui Mao ◽  
Lunhua Guo ◽  
Changming An ◽  
Cong Zhang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Cell Lines ◽  
Squamous Cell ◽  
Binding Protein ◽  
Neck Squamous Cell Carcinoma ◽  
Alternatively Spliced

Abstract Background: Head and neck squamous cell carcinoma (HNSCC) is a common cancer with high mortality. Anilin actin binding protein (ANLN) has been reported to be associated with carcinogenesis in multiple tumors. However, the expression pattern and functional effects of ANLN in HNSCC remains to be unclear.Methods: Expression of two major splice variants of ANLN was assessed in HNSCC tissues and cell lines. The functional effects and related mechanisms of ANLN isoforms were investigated in HNSCC in vitro and in vivo.Results: Our results showed that the two primary isoforms of ANLN transcripts ANLN-201 and ANLN-210 were highly expressed in HNSCC tissues and cell lines. Knockout of ANLN restrained cell proliferation, migration and invasion of SCC-9 cells. Mechanically, ANLN-201 could interact with c-Myc to keep its protein stability, thereby playing a oncogenic role in HNSCC. ANLN-210 could be transferred to macrophages via exosomes by binding to RNA binding protein hnRNPC. Exosomal ANLN-210 promoted macrophage polarization via PTEN/PI3K/Akt signaling pathway, thus stimulating tumor growth of HNSCC.Conclusions: Our findings demonstrate that alternatively spliced ANLN isoforms collaboratively promote HNSCC tumorigenesis in vitro and in vivo, which might provide the in-depth role and mechanism of ANLN in HNSCC development.

scholarly journals JOSD1 promotes proliferation and chemoresistance of head and neck squamous cell carcinoma under the epigenetic regulation of BRD4

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chao Jing ◽  
Dandan Liu ◽  
Qingchuan Lai ◽  
Linqi Li ◽  
Mengqian Zhou ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Gene Expression Omnibus ◽  
Neck Squamous Cell Carcinoma ◽  
The Cancer Genome Atlas ◽  
In Vivo Experiments

Abstract Background Deubiquitinating enzymes (DUBs) play critical roles in various cancers by modulating functional proteins post-translationally. Previous studies have demonstrated that DUB Josephin Domain Containing 1 (JOSD1) is implicated in tumor progression, however, the role and mechanism of JOSD1 in head and neck squamous cell carcinoma (HNSCC) remain to be explored. In this study, we aimed to identify the clinical significance and function of JOSD1 in HNSCC. Methods The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were analyzed to find novel DUBs in HNSCC. Immunohistochemistry assay was performed to determine the expression of JOSD1 in our cohort of 42 patients suffered with HNSCC. Kaplan–Meier analysis was used to identify the correlation between JOSD1 and the prognosis of HNSCC patients. The regulation of BRD4 on JOSD1 was determined by using pharmacological inhibition and gene depletion. The in vitro and in vivo experiments were conducted to elucidate the role of JOSD1 in HNSCC. Results The results of IHC showed that JOSD1 was aberrantly expressed in HNSCC specimens, especially in the chemoresistant ones. The overexpression of JOSD1 indicated poor clinical outcome of HNSCC patients. Moreover, JOSD1 depletion dramatically impaired cell proliferation and colony formation, and promoted cisplatin-induced apoptosis of HNSCC cells in vitro. Additionally, JOSD1 suppression inhibited the tumor growth and improved chemosensitivity in vivo. The epigenetic regulator BRD4 contributed to the upregulation of JOSD1 in HNSCC. Conclusions These results demonstrate that JOSD1 functions as an oncogene in HNSCC progression, and provide a promising target for clinical diagnosis and therapy of HNSCC.

scholarly journals Metformin as a senostatic drug enhances the anticancer efficacy of CDK4/6 inhibitor in head and neck squamous cell carcinoma

2020 ◽  
Vol 11 (10) ◽  
Author(s):  
Qinchao Hu ◽  
Jianmin Peng ◽  
Laibo Jiang ◽  
Wuguo Li ◽  
Qiao Su ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Xenograft Model ◽  
Neck Squamous Cell Carcinoma ◽  
In Vitro Assays ◽  
Anticancer Efficacy

Abstract CDK4/6 inhibitors show promising antitumor activity in a variety of solid tumors; however, their role in head and neck squamous cell carcinoma (HNSCC) requires further investigation. The senescence-associated secretory phenotype (SASP) induced by CDK4/6 inhibitors has dual effects on cancer treatment. The need to address the SASP is a serious challenge in the clinical application of CDK4/6 inhibitors. We investigated whether metformin can act as a senostatic drug to modulate the SASP and enhance the anticancer efficacy of CDK4/6 inhibitors in HNSCC. In this study, the efficacy of a combination of the CDK4/6 inhibitor LY2835219 and metformin in HNSCC was investigated in in vitro assays, an HSC6 xenograft model, and a patient-derived xenograft model. Senescence-associated β-galactosidase staining, antibody array, sphere-forming assay, and in vivo tumorigenesis assay were used to detect the impacts of metformin on the senescence and SASP induced by LY2835219. We found that LY2835219 combined with metformin synergistically inhibited HNSCC by inducing cell cycle arrest in vitro and in vivo. Metformin significantly modulated the profiles of the SASP elicited by LY2835219 by inhibiting the mTOR and stat3 pathways. The LY2835219-induced SASP resulted in upregulation of cancer stemness, while this phenomenon can be attenuated when combined with metformin. Furthermore, results showed that the stemness inhibition by metformin was associated with blockade of the IL6-stat3 axis. Survival analysis demonstrated that overexpression of IL6 and stemness markers was associated with poor survival in HNSCC patients, indicating that including metformin to target these proteins might improve patient prognosis. Collectively, our data suggest that metformin can act as a senostatic drug to enhance the anticancer efficacy of CDK4/6 inhibitors by reprogramming the profiles of the SASP.

Osimertinib and dihydroartemisinin: A novel drug combination targeting head and neck squamous cell carcinoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17526-e17526
Author(s):  
Rafael Rosell ◽  
Imane Chaib ◽  
Xueting Cai ◽  
David Llige ◽  
Mariacarmela Santarpia ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Molecular Mechanisms ◽  
Neck Squamous Cell Carcinoma ◽  
Signal Pathways ◽  
Synergistic Cytotoxicity

e17526 Background: Recurrent and metastatic head and neck squamous cell carcinoma (HNSCC) has a dismal prognosis with limited progression-free survival and overall survival, even when treated with different combinations of chemotherapy, targeted therapies and immunotherapy. We explored in vitro and in vivo the effect of the epidermal growth factor (EGFR) inhibitor, osimertinib, alone and in combination with dihydroartemisinin (DHA) in HNSCC. Methods: The combination of osimertinib with DHA was tested in the FaDu and CAL27 HNSCC cell lines. Tumor cell proliferation assays were conducted in cultured cells and mouse xenografts. Western blotting analysis of related signal pathways was performed to investigate the molecular mechanisms of the inhibitory effect of DHA and the combination. Other compounds, which inhibit signal transducer and activator of transcription 3 (STAT3), Src-family kinases (SFKs), sphingosine kinase 1 (SPHK1), or the receptor tyrosine kinase (RTK) AXL were also combined with osimertinib in vitro. Results: Osimertinib exerted synergistic cytotoxicity toward FaDu and CAL27 HNSCC cells when combined with DHA. DHA reversed the osimertinib-induced STAT3 and Src, phosphorylation. The double combination inhibited AXL expression. The anticancer potential of osimertinib plus DHA combination was validated in vivo on FaDu and CAL27 xenografts in mice without notable side effects. Conclusions: The results illustrate that the combinatory therapy of osimertinib and DHA, as a repurposing anticancer drug, could be a novel therapeutic strategy for recurrent and/or metastatic HNSCC patients. The findings indicate that a clinical trial is warranted to confirm the benefit of the combination.

scholarly journals Vandetanib Restores Head and Neck Squamous Cell Carcinoma Cells' Sensitivity to Cisplatin and Radiation In Vivo and In Vitro

2011 ◽  
Vol 17 (7) ◽  
pp. 1815-1827 ◽  
Author(s):  
Daisuke Sano ◽  
Fumihiko Matsumoto ◽  
David R. Valdecanas ◽  
Mei Zhao ◽  
David P. Molkentine ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Carcinoma Cells ◽  
Neck Squamous Cell Carcinoma

scholarly journals Radiosensitizing effect of galunisertib, a TGF-ß receptor I inhibitor, on head and neck squamous cell carcinoma in vitro

2022 ◽  
Author(s):  
Bernhard J. Jank ◽  
Teresa Lenz ◽  
Markus Haas ◽  
Lorenz Kadletz-Wanke ◽  
Nicholas J. Campion ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Cell Lines ◽  
Squamous Cell ◽  
Metabolic Activity ◽  
Neck Squamous Cell Carcinoma ◽  
Radiosensitizing Effect

SummaryBackground. Resistance to radiation therapy poses a major clinical problem for patients suffering from head and neck squamous cell carcinoma (HNSCC). Transforming growth factor ß (TGF-ß) has emerged as a potential target. This study aimed to investigate the radiosensitizing effect of galunisertib, a small molecule TGF-ß receptor kinase I inhibitor, on HNSCC cells in vitro. Methods. Three HNSCC cell lines were treated with galunisertib alone, or in combination with radiation. Of those three cell lines, one has a known inactivating mutation of the TGF-ß pathway (Cal27), one has a TGF-ß pathway deficiency (FaDu) and one has no known alteration (SCC-25). The effect on metabolic activity was evaluated by a resazurin-based reduction assay. Cell migration was evaluated by wound-healing assay, clonogenic survival by colony formation assay and cell cycle by FACS analysis. Results. Galunisertib reduced metabolic activity in FaDu, increased in SCC-25 and had no effect on CAL27. Migration was significantly reduced by galunisertib in all three cell lines and showed additive effects in combination with radiation in CAL27 and SCC-25. Colony-forming capabilities were reduced in SCC-25 by galunisertib and also showed an additive effect with adjuvant radiation treatment. Cell cycle analysis showed a reduction of cells in G1 phase in response to galunisertib treatment. Conclusion. Our results indicate a potential antineoplastic effect of galunisertib in HNSCC with intact TGF-ß signaling in combination with radiation.

Sign in / Sign up

Export Citation Format

Share Document