The PI3K /Akt/ mTORC signaling axis in head and neck squamous cell carcinoma: Possibilities for therapeutic interventions either as single agents or in combination with conventional therapies

IUBMB Life ◽  
2021 ◽  
Author(s):  
Nader Akbari Dilmaghani ◽  
Ava Safaroghli‐Azar ◽  
Atieh Pourbagheri‐Sigaroodi ◽  
Davood Bashash
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Therapeutic Interventions ◽  
Signaling Axis

scholarly journals Expression of the Extracellular Sulfatase SULF2 Affects Survival of Head and Neck Squamous Cell Carcinoma Patients

2021 ◽  
Vol 10 ◽  
Author(s):  
Yang Yang ◽  
Jaeil Ahn ◽  
Rekha Raghunathan ◽  
Bhaskar V. Kallakury ◽  
Bruce Davidson ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Hpv Infection ◽  
Neck Squamous Cell Carcinoma ◽  
Therapeutic Interventions ◽  
Tumor Tissues ◽  
Significant Difference

Sulfation of heparan sulfate proteoglycans (HSPG) regulates signaling of growth factor receptors via specific interactions with the sulfate groups. 6-O-Sulfation of HSPG is an impactful modification regulated by the activities of dedicated extracellular endosulfatases. Specifically, extracellular sulfatase Sulf-2 (SULF2) removes 6-O-sulfate from HS chains, modulates affinity of carrier HSPG to their ligands, and thereby influences activity of the downstream signaling pathway. In this study, we explored the effect of SULF2 expression on HSPG sulfation and its relationship to clinical outcomes of patients with head and neck squamous cell carcinoma (HNSCC). We found a significant overexpression of SULF2 in HNSCC tumor tissues which differs by tumor location and etiology. Expression of SULF2 mRNA in tumors associated with human papillomavirus (HPV) infection was two-fold lower than in tumors associated with a history of tobacco and alcohol consumption. High SULF2 mRNA expression is significantly correlated with poor progression-free interval and overall survival of patients (n = 499). Among all HS-related enzymes, SULF2 expression had the highest hazard ratio in overall survival after adjusting for clinical characteristics. SULF2 protein expression (n = 124), determined by immunohistochemical analysis, showed a similar trend. The content of 6-O-sulfated HSPG, measured by staining with the HS3A8 antibody, was higher in adjacent mucosa compared to tumor tissue but revealed no difference based on SULF2 staining. LC-MS/MS analysis showed low abundance of N-sulfation and O-sulfation in HS but no significant difference between SULF2-positive and SULF2-negative tumors. Levels of enzymes modifying 6-O-sulfation, measured by RT-qPCR in HNSCC tumor tissues, suggest that HSPG sulfation is carried out by the co-regulated activities of multiple genes. Imbalance of the HS modifying enzymes in HNSCC tumors modifies the overall sulfation pattern, but the alteration of 6-O-sulfate is likely non-uniform and occurs in specific domains of the HS chains. These findings demonstrate that SULF2 expression correlates with survival of HNSCC patients and could potentially serve as a prognostic factor or target of therapeutic interventions.

scholarly journals The circ_0032822 Promotes the Proliferation of Head and Neck Squamous Cell Carcinoma Cells Through miR-141/EF3 Signaling Axis

2021 ◽  
Vol 11 ◽  
Author(s):  
Shuajia Zhang ◽  
Jiahui Han ◽  
Jing Fu
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Tumor Tissues ◽  
Mechanistic Analysis ◽  
Repressive Effect ◽  
Signaling Axis

Head and neck squamous cell carcinoma (HNSCC) refers to an epithelial malignant tumor that originates in the head and neck, and over 600,000 new cases are reported every year, However, the overall prognosis is still poor due to local recurrence and distant metastasis after surgery. The circ_0032822 has been reported upregulated in human oral squamous cell carcinoma; however, the detailed function or mechanism remains unknown. In this study, we confirmed the upregulation of circ_0032822 in HNSCC tumor tissues. Functionally, the overexpression of circ_0032822 significantly promoted the proliferation of HNSCC cell lines along with the S phase arrest and reduced apoptosis, while downregulation of circ_0032822 has the opposite effect in vitro. Mechanistic analysis showed that circ_0032822 acted as a competing endogenous RNA of miR-141 to diminish the repressive effect of miR-141 on its target E2F3. In conclusion, we demonstrated that circ_0032822 functions as a tumor oncogene in HNSCC and that its function is regulated via the miR-141/E2F3 axis.

scholarly journals CircRNA_ACAP2 Suppresses EMT in Head and Neck Squamous Cell Carcinoma by Targeting the miR-21-5p/STAT3 Signaling Axis

2020 ◽  
Vol 10 ◽  
Author(s):  
Chuan Ma ◽  
Tingting Shi ◽  
Zhuli Qu ◽  
Aobo Zhang ◽  
Zuping Wu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Binding Sites ◽  
Specific Binding ◽  
Neck Squamous Cell Carcinoma ◽  
Specific Binding Sites ◽  
Stat3 Signaling ◽  
Signaling Axis

Circular RNAs (circRNAs) contain microRNA (miRNA)-specific binding sites and can function as miRNA sponges to regulate gene expression by suppressing the inhibitory effect of miRNAs on their target genes. MiR-21-5p has been reported to be involved in the development of head and neck squamous cell carcinoma (HNSCC) and plays an important role in the activation of epithelial-mesenchymal transition (EMT). However, the upstream regulatory mechanism and downstream targets of miR-21-5p in tumor cells remain unknown. CircRNA_ACAP2 inhibits the function of miR-21-5p by binding to its specific binding sites in HNSCC cells. Overexpression of CircRNA_ACAP2 inhibits the proliferation and migration of HNSCC cells, while downregulation of CircRNA_ACAP2 has the opposite effect. STAT3 is a direct target gene of miR-21-5p and a transcription factor of ZEB1. We demonstrate that CircRNA_ACAP2 functions as a tumor suppressor gene in HNSCC and that its function is regulated via the miR-21-5p/STAT3 signaling axis.

Head and Neck Squamous Cell Carcinoma: Prognosis using molecular approach

2014 ◽  
Vol 9 (6) ◽  
pp. 593-613
Author(s):  
Tarikul Mazumder ◽  
Sayantan Nath ◽  
Nibendu Nath ◽  
Munish Kumar
Keyword(s):  
Squamous Cell Carcinoma ◽  
Dna Repair ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
P53 Gene ◽  
Neck Squamous Cell Carcinoma ◽  
Therapeutic Interventions ◽  
P53 Gene Mutation ◽  
Etiological Agents

AbstractHead and neck squamous cell carcinoma (HNSCC) is the fifth most prevalent cancer worldwide. Apart from various known clinicopathogical factors, it is still a major concern as many genetic and epigenetic alterations bring about the possibility of this deadly disease. The aim of this review is to explore the possible role of DNA repair pathways and the polymorphic status of DNA repair genes (XPA, XPC, XPD, XRCC1 and XRCC3) in the onset of HNSCC, along with sequence variations in genes such as Glutathione S-transferases (GSTT1, M1 and P1) that are significantly associated with HNSCC risk. We also focus on the p53 gene mutation induced by various etiological agents and threat factors with its implications towards HNSCC, and emphasise the current therapeutic interventions in treating HNSCC.

scholarly journals Tumor microenvironment: an evil nexus promoting aggressive head and neck squamous cell carcinoma and avenue for targeted therapy

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Ajaz A. Bhat ◽  
Parvaiz Yousuf ◽  
Nissar A. Wani ◽  
Arshi Rizwan ◽  
Shyam S. Chauhan ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Tumor Microenvironment ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Epithelial Mesenchymal Transition ◽  
Critical Role ◽  
Neck Squamous Cell Carcinoma ◽  
Therapeutic Interventions ◽  
Mesenchymal Transition

AbstractHead and neck squamous cell carcinoma (HNSCC) is a very aggressive disease with a poor prognosis for advanced-stage tumors. Recent clinical, genomic, and cellular studies have revealed the highly heterogeneous and immunosuppressive nature of HNSCC. Despite significant advances in multimodal therapeutic interventions, failure to cure and recurrence are common and account for most deaths. It is becoming increasingly apparent that tumor microenvironment (TME) plays a critical role in HNSCC tumorigenesis, promotes the evolution of aggressive tumors and resistance to therapy, and thereby adversely affects the prognosis. A complete understanding of the TME factors, together with the highly complex tumor–stromal interactions, can lead to new therapeutic interventions in HNSCC. Interestingly, different molecular and immune landscapes between HPV+ve and HPV−ve (human papillomavirus) HNSCC tumors offer new opportunities for developing individualized, targeted chemoimmunotherapy (CIT) regimen. This review highlights the current understanding of the complexity between HPV+ve and HPV−ve HNSCC TME and various tumor–stromal cross-talk modulating processes, including epithelial–mesenchymal transition (EMT), anoikis resistance, angiogenesis, immune surveillance, metastatic niche, therapeutic resistance, and development of an aggressive tumor phenotype. Furthermore, we summarize the recent developments and the rationale behind CIT strategies and their clinical applications in HPV+ve and HPV−ve HNSCC.

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