scholarly journals The role of acetyl-coA carboxylase2 in head and neck squamous cell carcinoma

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7037 ◽  
Author(s):  
Kun Li ◽  
Chengcheng Zhang ◽  
Lei Chen ◽  
Pingping Wang ◽  
Yang Fang ◽  
...  

Background Acetyl-CoA carboxylase (ACC) plays an important role in the metabolism of various cancer cells, but its role in head and neck squamous cell carcinoma (HNSCC) is uncertain. Therefore, in the present study, we explored the role of ACC2 in HNSCC. Methods Western blot and immunohistochemistry assays were used to determine ACC2 protein expression levels in laryngocarcinoma and adjacent normal tissues derived from patients with laryngocarcinoma. ACC2 expression was knocked down in the hypopharyngeal cancer cell line FaDu to determine its effect on apoptosis. Lipid oil red staining was used to test the change of intracellular lipid. Results The results showed that the ACC2 protein was highly expressed in laryngocarcinoma and that the ACC2 expression level was positively associated with the clinical cancer stage and negatively associated with the degree of laryngocarcinoma cell differentiation. Kaplan–Meier analyses indicated that compared with patients having low levels of ACC2, those with high ACC2 levels had a decreased 5-year survival rate. The results of western blot and terminal deoxynucleotidyl transferase dUTP nick-end labeling assays showed that knockdown of ACC2 accelerated apoptosis in FaDu cells. Furthermore, knockdown of ACC2 significantly reduced the intracellular lipid levels in FaDu cells. Conclusion These findings suggest that ACC2 may be an important prognostic marker for patients with HNSCC and that ACC2 may be a potential target in the treatment of HNSCC.

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Areeg Elmusrati ◽  
Justin Wang ◽  
Cun-Yu Wang

AbstractHead and neck squamous cell carcinoma (HNSCC), an aggressive malignancy, is characterized by high morbidity and low survival rates with limited therapeutic options outside of regional surgery, conventional cytotoxic chemotherapy, and irradiation. Increasing studies have supported the synergistic role of the tumor microenvironment (TME) in cancer advancement. The immune system, in particular, plays a key role in surveillance against the initiation, development, and progression of HNSCC. The understanding of how neoplastic cells evolve and evade the immune system whether through self-immunogenicity manipulation, or expression of immunosuppressive mediators, provides the foundation for the development of advanced therapies. Furthermore, the crosstalk between cancer cells and the host immune system have a detrimental effect on the TME promoting angiogenesis, proliferation, and metastasis. This review provides a recent insight into the role of the key inflammatory cells infiltrating the TME, with a focus on reviewing immunological principles related to HNSCC, as cancer immunosurveillance and immune escape, including a brief overview of current immunotherapeutic strategies and ongoing clinical trials.


2006 ◽  
Vol 6 (9) ◽  
pp. 1195-1203 ◽  
Author(s):  
Ralph Pries ◽  
Stefan Nitsch ◽  
Barbara Wollenberg

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiang Wu ◽  
Jin Li ◽  
Tingyuan Yan ◽  
Xueping Ke ◽  
Xin Li ◽  
...  

Abstract Background The homeobox gene Homeobox B7 (HOXB7) is overexpressed across a range of cancers and promotes tumorigenesis through varying effects on proliferation, survival, migration and invasion. However, its expression pattern and oncogenic role of HOXB7 in head and neck squamous cell carcinoma (HNSCC) remain largely unexplored. Here, we aimed to explore the expression pattern of HOXB7, its clinical significance as well as functional roles in HNSCC. Methods HOXB7 mRNA expression in HNSCC was determined by data mining and analyses from TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus) datasets. The protein abundance of HOXB7 was measured by immunohistochemistry in 119 primary HNSCC samples and associations between its expression and clinicopathological parameters and patient survival were evaluated. The pro-tumorigenic roles of HOXB7 in HNSCC were further delineated in vitro by loss-of-function assay. And a xenograft tumor model was established in nude mice to assess the role of HOXB7 in tumor growth. Connectivity Map (CMap) analysis was performed to identify bioactive small molecules which might be potential inhibitors for HOXB7. Results Bioinformatics analyses showed that HOXB7 mRNA was significantly overexpressed in 8 independent HNSCC datasets from TCGA and GEO databases. HOXB7 protein was markedly upregulated in HNSCC samples as compared to normal counterparts and its overexpression significantly associated with high pathological grade, advanced clinical stage, cervical node metastasis (P = 0.0195, 0.0152, 0.0300) and reduced overall and disease-free survival (P = 0.0014, 0.0007). Univariate and multivariate Cox regression analyses further revealed HOXB7 as an independent prognostic factor for patients’ overall survival. Moreover, HOXB7 knockdown significantly inhibited cell proliferation, migration and invasion and induced cell apoptosis in HNSCC cells, and resulted in compromised tumour growth in vivo. Furthermore, CMap (Connectivity map) analysis has identified three potential bioactive small molecule inhibitors (NU-1025, thiamine, vinburnine) for HOXB7 targeted therapy in HNSCC. Conclusions Our findings revealed that overexpression of HOXB7 was associates with tumour aggressiveness and unfavourable prognosis by serving a novel prognostic biomarker in HNSCC. Moreover, HOXB7 might be involved in the development and progression of HNSCC as an oncogene, and thereby might be a potential therapeutic target for HNSCC.


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