Notch Signalling: A Potential Therapeutic Pathway in Oral Squamous Cell Carcinoma

2021 ◽  
Vol 21 ◽  
Author(s):  
Ankit Pandey ◽  
Sreeshma Bhuvanadas ◽  
Joel P. Joseph ◽  
Rama Jayaraj ◽  
Arikketh Devi
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Tumour Progression ◽  
Notch Signalling ◽  
Signalling Pathway ◽  
Notch Signalling Pathway ◽  
Mortality And Morbidity ◽  
Cellular Dysfunction

: Cancer, a set of diseases characterized by abnormal cell growth resulting from alteration in the expression pattern of diverse genes, is one of the prominent cause of mortality and morbidity worldwide. This modification of various genes lead to altered signalling cascades and changes in the molecular network. These changes eventually give rise to cellular dysfunction and then to systemic failure causing death. Of the several pathways that are aberrantly activated in cancer, Notch signalling pathway is a prominent one. Notch signalling pathway is a juxtracrine signalling pathway which activates the genes associated with cell proliferation, survival and angiogenesis. Notch signalling pathway components are seen to be upregulated in several types of cancer. Oral squamous cell carcinoma (OSCC) is a predominant category of oral cancer where aberrant activation of Notch signalling causes tumour progression and metastasis. In this review, we discuss the Notch signalling pathway, its components, forms and its role in the progression and metastasis of oral squamous cell carcinoma.

Fibroblast gene expression profile reflects the stage of tumour progression in oral squamous cell carcinoma

2011 ◽  
Vol 223 (4) ◽  
pp. 459-469 ◽  
Author(s):  
Kue Peng Lim ◽  
Nicola Cirillo ◽  
Yazan Hassona ◽  
Wenbin Wei ◽  
Johanna K Thurlow ◽  
...  
Keyword(s):  
Gene Expression ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Squamous Cell ◽  
Tumour Progression

Zinc finger AN1-type containing 4 is a novel marker for predicting metastasis and poor prognosis in oral squamous cell carcinoma

2017 ◽  
Vol 71 (5) ◽  
pp. 436-441 ◽  
Author(s):  
Miyako Kurihara-Shimomura ◽  
Tomonori Sasahira ◽  
Hiroshi Nakamura ◽  
Chie Nakashima ◽  
Hiroki Kuniyasu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Zinc Finger ◽  
Squamous Cell ◽  
Poor Prognosis ◽  
Proportional Hazards Model ◽  
Tumour Progression ◽  
Cox Proportional Hazards Model ◽  
Poor Prognostic Factor

AimsHead and neck cancer, including oral squamous cell carcinoma (OSCC), is the sixth most common cancer worldwide and has a high potential for locoregional invasion and nodal metastasis. Therefore, discovery of a useful molecular biomarker capable of predicting tumour progression and metastasis of OSCC is crucial. We have previously reported zinc finger AN1-type containing 4 (ZFAND4) as one of the most upregulated genes in recurrent OSCC using a cDNA microarray analysis. Although ZFAND4 has been shown to promote cell proliferation of gastric cancer, its expression and clinicopathological roles in OSCC remain unclear.MethodsIn this study, we examined ZFAND4 expression by immunohistochemistry in 214 cases of OSCC.ResultsHigh cytoplasmic expression of ZFAND4 was observed in 45 out of 214 (21%) patients with OSCC. Expression levels of ZFAND4 were strongly associated with metastasis to the lymph nodes (p=0.0429) and distant organs (p=0.0068). Cases with high expression of ZFAND4 had a significantly unfavourable prognosis compared with patients with low expression of ZFAND4 (p<0.0001). Furthermore, ZFAND4 overexpression was an independent poor prognostic factor for OSCC as determined by multivariate analysis using the Cox proportional hazards model (p<0.0001).ConclusionsThese results suggest that ZFAND4 is a useful marker for predicting metastasis and poor prognosis in patients with OSCC.

scholarly journals Prognostic significance of Cep55 in oral squamous cell carcinoma

2018 ◽  
Vol 3 ◽  
pp. 2057178X1878197
Author(s):  
L Surendra ◽  
Vanishri C Haragannavar ◽  
Roopa S Rao ◽  
Kavitha Prasad ◽  
SV Sowmya ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Early Stage ◽  
Prognostic Significance ◽  
Clinical Staging ◽  
Biological Behaviour ◽  
Treatment Protocols ◽  
Mortality And Morbidity

Objective: Currently, oral squamous cell carcinoma (OSCC) is one of the most fatal cancers of all head and neck malignancies. Despite advancements in therapy, the mortality and morbidity remain high. Hence, it is essential to identify useful prognostic markers for high-risk individuals with OSCC to decide on treatment protocols. Centrosomal protein 55 ( Cep55), a regulator of the cell cycle, has been considered to play a role in carcinogenesis. Although there are numerous studies on its role in various other epithelial cancers such as breast, ovarian and lung cancers, its significance in the behaviour of OSCC is yet to be studied. The present study aimed to study Cep55 expression in OSCC and correlate with the tumour characteristics and patient survival. Materials and Methods: Forty pathologically diagnosed cases of OSCC were included in the study: 20 each of early and advanced OSCC cases. Formalin-fixed paraffin-embedded archival samples were used. The sections were immunohistochemically stained with Cep55 antibody. The expression levels of Cep55 were correlated with clinical parameters and disease outcome. Results: A higher expression of Cep55 was observed in advanced stage compared to early stage of OSCC. The Cep55 expression showed no significant relation with respect to clinical staging, pathological grading and site, except for tongue. Cep55 overexpression is significantly associated with poor survival. Conclusion: The present study suggests that Cep55 could play an important role in determining the biological behaviour and survival of OSCC patients independent of tumour staging and pathological grading. Thus, assessment of Cep55 expression could navigate the surgeons to plan an appropriate treatment.

scholarly journals Intersecting Mechanisms of Hypoxia and Prostaglandin E2-Mediated Inflammation in the Comparative Biology of Oral Squamous Cell Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Walaa Hamed Shaker Nasry ◽  
Chelsea K. Martin
Keyword(s):  
Squamous Cell Carcinoma ◽  
Arachidonic Acid ◽  
Oral Squamous Cell Carcinoma ◽  
Prostaglandin E2 ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Tumour Progression ◽  
Low Oxygen ◽  
Acid Pathway ◽  
Arachidonic Acid Pathway

The importance of inflammation in the pathogenesis of cancer was first proposed by Rudolph Virchow over 150 years ago, and our understanding of its significance has grown over decades of biomedical research. The arachidonic acid pathway of inflammation, including cyclooxygenase (COX) enzymes, PGE2 synthase enzymes, prostaglandin E2 (PGE2) and PGE2 receptors has been extensively studied and has been associated with different diseases and different types of cancers, including oral squamous cell carcinoma (OSCC). In addition to inflammation in the tumour microenvironment, low oxygen levels (hypoxia) within tumours have also been shown to contribute to tumour progression. Understandably, most of our OSCC knowledge comes from study of this aggressive cancer in human patients and in experimental rodent models. However, domestic animals develop OSCC spontaneously and this is an important, and difficult to treat, form of cancer in veterinary medicine. The primary goal of this review article is to explore the available evidence regarding interaction between hypoxia and the arachidonic acid pathway of inflammation during malignant behaviour of OSCC. Overlapping mechanisms in hypoxia and inflammation can contribute to tumour growth, angiogenesis, and, importantly, resistance to therapy. The benefits and controversies of anti-inflammatory and anti-angiogenic therapies for human and animal OSCC patients will be discussed, including conventional pharmaceutical agents as well as natural products.

scholarly journals Secreted Protein Markers in Oral Squamous Cell Carcinoma (Oscc)

2021 ◽  
Author(s):  
Madiha Mumtaz ◽  
Irene V Bijnsdorp ◽  
Franziska Böttger ◽  
Sander R Piersma ◽  
Thang V Pham ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Protein Localization ◽  
Cancer Cell Line ◽  
P Value ◽  
Protein Markers ◽  
Mortality And Morbidity ◽  
Non Invasive

Abstract Background Oral squamous cell carcinoma (OSCC) is a main cause of oral cancer mortality and morbidity in central south Asia. To improve the clinical outcome of OSCC patients, early detection markers are needed, which are preferably non-invasive and thus independent of a tissue biopsy. Methods In the present study, we aimed to identify robust candidate protein biomarkers for early OSCC diagnosis. To this end, we measured the global protein profiles of OSCC tissue lysates to matched normal adjacent mucosa samples (n=14) and the secretomes of nine HNSCC cell lines using LC-MS/MS-based proteomics. Results A total of 5,123 tissue proteins were identified, of which 205 were robustly up- regulated (p-value <0.01, fold change ˃+2) in OSCC-tissues compared to normal tissues. The biological process “Secretion” was highly enriched in this set of proteins. Other upregulated biological pathways included “Unfolded Protein Response”, “Spliceosomal complex assembly”, “Protein localization to endosome” and “Interferon Gamma Response”. Transcription factor analysis implicated Creb3L1, ESRRA, YY, ELF2, STAT1 and XBP as potential regulators. Of the 205 upregulated tissue proteins, 132 were identified in the cancer cell line secretomes, underscoring their potential use as non-invasive biofluid markers. To further prioritize our candidate markers for non-invasive OSCC detection, we integrated our data with public biofluid datasets including OSCC saliva, yielding 25 candidate markers for further study. Conclusions We identified several key proteins and processes that are associated with OSCC tissues, underscoring the importance of altered secretion. Cancer-associated OSCC secretome proteins present in saliva have potential to be used as novel non-invasive biomarkers for the early diagnosis of OSCC.

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