scholarly journals TRPA1: A Potential Prognostic Indicator for Oral Squamous Cell Carcinoma

2021 ◽  
Author(s):  
Rajdeep Chakraborty ◽  
Amara Jabeen ◽  
Honghua Hu ◽  
Charbel Darido ◽  
Karen Vickery ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Cancer ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cancer Cells ◽  
Cell Lines ◽  
Squamous Cell ◽  
Cannabinoid Receptors ◽  
Prognostic Indicator ◽  
Oral Cancer Cells

Introduction: Transient receptors are related to oral cancer pain. Previously capsaicin (TRPV1 agonist) was shown to induce cell death in oral cancer cells. We hypothesised that these receptors are present in oral cancer. Method: We examined the presence of cannabinoid receptors (CB1 and CB2) and targets (TRPV1, TRPA1, CaV 3.1, CaV 3.2, CaV 3.3) via quantitative polymerase chain reaction (qPCR) in oral cancer cells SCC4, SCC9, SCC25, Cal27, and normal oral cell line OKF6. Result: Cannabinoid receptors are absent in all the cell lines, while TRPA1 is only present in normal cells, but absent in all the oral cancer cell lines. Voltage-gated calcium channels are present in all the cell lines. Conclusion and Future Aspects: TRPA1 could be the possible future prognostic indicator of oral squamous cell carcinoma. Future functionality assays could use precancerous cell lines to follow the loss of TRPA1.

scholarly journals Stem Cell Markers CXCR-4 and CD133 Predict Aggressive Phenotype and Their Double Positivity Indicates Poor Prognosis of Oral Squamous Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 5895
Author(s):  
Ravindran Caspa Gokulan ◽  
Halagowder Devaraj
Keyword(s):  
Squamous Cell Carcinoma ◽  
Stem Cell ◽  
Oral Cancer ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cancer Cells ◽  
Cell Lines ◽  
Squamous Cell ◽  
Poor Prognosis ◽  
Oral Cancer Cells

The activation of the SDF-1/CXCR-4 pathway is crucial for the invasion and metastasis of oral cancer cells. The CXCR-4 positive cells possess stem cell characteristics and express the cancer stem cell marker, CD133, in tumors of colon and pancreas. Despite several studies, the co-expression of CXCR-4 and CD133 and its significance is still largely unknown in oral cancer. Therefore, we aimed to investigate the impact of CXCR-4 and CD133 double positivity in the prognosis of oral cancer. The significance of PKC-δ, one of the key signaling molecules that regulates CXCR-4, was also analyzed. Immunohistochemistry and double immunofluorescence was used to investigate the co-localization of CXCR-4, PKC-δ and CD133 in the human tissues and cell lines of oral squamous cell carcinoma. The expression of CXCR-4, PKC-δ and CD133 were found to be higher in poorly differentiated and lymph node metastasis-positive cases. Interestingly, CXCR-4 positive cells showed positive staining for PKC-δ and CD133 in oral cancer tissue and cell lines. Moreover, CXCR-4+/CD133+ and CXCR-4+/PKC-δ+ double positive cases have the worst survival. We discovered, for the first time, that patients with expression of both CXCR-4 and CD133 have a lower survival rate, and CXCR-4+/CD133+, as well as CXCR-4+/PKC-δ+ double positivity, can be utilized to predict poor prognosis. CXCR-4, PKC-δ and CD133 might regulate aggressiveness and invasion of oral cancer cells.

scholarly journals MicroRNA-143 suppresses oral squamous cell carcinoma cell growth, invasion and glucose metabolism through targeting hexokinase 2

2017 ◽  
Vol 37 (3) ◽  
Author(s):  
Xianghui Sun ◽  
Lei Zhang
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Migration ◽  
Glucose Metabolism ◽  
Oral Cancer ◽  
Tumor Suppressor ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cancer Cells ◽  
Cell Lines ◽  
Oral Cancer Cells

miRNAs are non-coding RNAs that have functions to regulate gene expression and play essential roles in a variety of biological processes of cancers. In the present study, we report miR-143 acts as a tumor suppressor in human oral squamous cell carcinoma (OSCC). The expressions of miR-143 are down-regulated in both OSCC cell lines and patient samples compared with normal adjacent tissues. We found overexpression of miR-143 in oral cancer cell lines suppresses cell migration, cellular glucose metabolism and proliferation. Moreover, overexpression of miR-143 promoted apoptosis and significantly caused cell cycle arrest at G1 stage. The colony formation of oral cancer cells was also suppressed by miR-143. We identified hexokinase 2 (HK2) as a direct target of miR-143 in oral cancer cells. Our data show that miR-143 complementary pairs to the 3′-UTR of HK2 in oral cancer cells, leading to the inhibition of glycolysis in vitro and in vivo. Moreover, knockdown of HK2 by siRNA in oral cancer cells inhibited glucose metabolism, proliferation and migration. Recovery of glucose metabolism by overexpression of HK2 in miR-143 overexpressing cells restores the cell migration and proliferation, suggesting that the miR-143-mediated cancer suppression is through the direct inhibition of HK2. In summary, the present studies highlight miR-143 as a tumor suppressor in OSCC by the suppression of cell migration, glucose metabolism and proliferation through directly targeting HK2, rendering miR-143 a therapeutic strategy for the treatment of clinical OSCC patients.

scholarly journals MiR-1254 Functions as a Tumor Suppressor in Oral Squamous Cell Carcinoma by Targeting CD36

2019 ◽  
Vol 18 ◽  
pp. 153303381985944 ◽  
Author(s):  
Ruixue Chen ◽  
Yang Zhang ◽  
Xudong Zhang
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Cancer ◽  
Tumor Suppressor ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cancer Cells ◽  
Squamous Cell ◽  
Luciferase Reporter ◽  
Oral Cancer Cells ◽  
Proliferation And Invasion

Oral squamous cell carcinoma is one of the most common cancers around the world. The patients with oral squamous cell carcinoma are often diagnosed at late stages, leading to unfavorable prognosis. MicroRNAs might function as oncogenes or tumor suppressor genes in the tumorigenesis of cancer. This study aimed to explore the role of miR-1254 in oral squamous cell carcinoma. We examined the expression levels of miR-1254 in oral squamous cell carcinoma tissue samples and cell line.Proliferation and invasion assays were performed in oral squamous cell carcinoma cells with miR-1254 overexpression or underexpression. The potential regulatory mechanisms were also explored. We found that miR-1254 was significantly reduced in oral squamous cell carcinoma tissues and cell lines. In addition, downregulation of miR-1254 in oral squamous cell carcinoma tumor tissues was closely associated with cancer staging and lymph node metastasis. Enforced expression of miR-1254 significantly inhibited proliferation and invasion in oral cancer cells, and downregulation of miR-1254 promoted the oncogenic activities of oral cancer cells. CD36 was identified as a direct downstream target of miR-1254 by the luciferase reporter assay. Overexpression of CD36 partially restored the proliferation and invasion capacity inhibited by miR-1254. CD36 expression was inversely correlated with miR-1254 expression in the oral squamous cell carcinoma tissues. Taken together, our study provided the compelling evidence that miR-1254 might inhibit the progression of OSCC by partially downregulating CD36, and restoration of miR-1254 may represent an effective strategy for treating oral squamous cell carcinoma.

scholarly journals Association of ATG4B and Phosphorylated ATG4B Proteins with Tumorigenesis and Prognosis in Oral Squamous Cell Carcinoma

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1854 ◽  
Author(s):  
Pei-Feng Liu ◽  
Hung-Chih Chen ◽  
Jin-Shiung Cheng ◽  
Wei-Lun Tsai ◽  
Huai-Pao Lee ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Oral Cancer ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cancer Cells ◽  
Squamous Cell ◽  
Migration And Invasion ◽  
Protein Levels ◽  
Oral Cancer Cells

Oral squamous cell carcinoma (OSCC) is one of the major leading causes of cancer death worldwide due to the limited availability of biomarkers and therapeutic targets. Autophagy related protease 4B (ATG4B) is an essential protease for the autophagy machinery, and ATG4B phosphorylation at Ser383/392 increases its proteolytic activity. ATG4B expression and activation are crucial for cancer cell proliferation and invasion. However, the clinical relevance of ATG4B and phospho-Ser383/392-ATG4B for OSCC remains unknown, particularly in buccal mucosal SCC (BMSCC) and tongue SCC (TSCC). With a tissue microarray comprising specimens from 498 OSCC patients, including 179 BMSCC and 249 TSCC patients, we found that the protein levels of ATG4B and phospho-Ser383/392-ATG4B were elevated in the tumor tissues of BMSCC and TSCC compared with those in adjacent normal tissues. High protein levels of ATG4B were significantly associated with worse disease-specific survival (DSS) in OSCC patients, particularly in patients with tumors at advanced stages. In contrast, phospho-Ser383/392-ATG4B expression was correlated with poor disease-free survival (DFS) in TSCC patients. Moreover, ATG4B protein expression was positively correlated with phospho-Ser383/392-ATG4B expression in both BMSCC and TSCC. However, high coexpression levels of ATG4B and phospho-Ser383/392-ATG4B were associated with poor DFS only in TSCC patients, whereas they had no significant association with DSS in BMSCC and TSCC patients. In addition, silencing ATG4B with an antisense oligonucleotide (ASO) or small interfering RNA (siRNA) diminished cell proliferation of TW2.6 and SAS oral cancer cells. Further, knockdown of ATG4B reduced cell migration and invasion of oral cancer cells. Taken together, these findings suggest that ATG4B might be a biomarker for diagnosis/prognosis of OSCC and a potential therapeutic target for OSCC patients.

Targeting CD47 Inhibits Tumor Development and Increases Phagocytosis in Oral Squamous Cell Carcinoma

2020 ◽  
Vol 20 ◽  
Author(s):  
Xiao-Jing Ye ◽  
Jian-Guang Yang ◽  
Ya-Qin Tan ◽  
Xiao-Jie Chen ◽  
Gang Zhou
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Cancer ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cancer Cells ◽  
Squamous Cell ◽  
Tumor Development ◽  
Migration And Invasion ◽  
Oral Cancer Cells ◽  
Underlying Mechanisms

Background: Our previous work demonstrated upregulated CD47 in oral squamous cell carcinoma (OSCC). Objective: In the present study,we aimed to investigate the effects of CD47 on tumor cell development and phagocytosis in OSCC and elucidate the underlying mechanisms. Methods: The proliferation, apoptosis, migration, and invasion of oral cancer cells were analyzed after knocking down the expression of CD47. The effects of CD47 on tumor development were also evaluated using a murine model of OSCC. The involvement of CD47 in the phagocytosis of oral cancer cells was identified. Results: Cell proliferation was suppressed by knocking down the expression of CD47 in human OSCC cell line Cal-27 cells but there was no change in theapoptosis rate. Moreover, impaired expression of CD47 inhibited the migration and invasion of Cal-27 cells. Furthermore, we found that nude mice injected with CD47 knocked-down Cal-27 cells displayed decreased tumor volumes at week 9 compared to xenograft transplantations of blank Cal-27 cells. In addition, in vitrophagocytosis of Cal-27 cells by macrophages was significantly enhanced after the knockdown of CD47, which positively correlated with compromised STAT3/JAK2 signaling. Conclusion: In summary, the knockdown of CD47 down regulated the development of OSCC and increased the phagocytosis of Cal-27 cells, indicating that CD47 might be a promising therapeutic target.

scholarly journals Inhibition of Cell Proliferation and MAP Kinase and Akt Pathways in Oral Squamous Cell Carcinoma by Genistein and Biochanin A

2010 ◽  
Vol 7 (3) ◽  
pp. 351-358 ◽  
Author(s):  
Tara L. Johnson ◽  
Maria B. Lai ◽  
James C. K. Lai ◽  
Alok Bhushan
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Oral Cancer ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Signaling Pathways ◽  
Cell Lines ◽  
Squamous Cell ◽  
Biochanin A ◽  
High Morbidity

High morbidity and mortality associated with oral squamous cell carcinoma (OSCC) are largely attributable to late stage diagnosis. Despite significant advances in therapeutic strategies, the five-year survival rate for oral cancer remains at about 50%. A chemopreventive approach may be an effective alternative or adjunct to current therapies. Previous studies have shown anti-tumor effects of isoflavones in several cancers, including oral cancer. However, their mechanisms of action are still unclear. We hypothesized that isoflavones inhibit multiple signaling pathways implicated in oral carcinogenesis. To address our hypothesis, we investigated the effects of three isoflavone derivatives, genistein, biochanin A and daidzein, on SCC15 and SCC25 squamous cell carcinoma cell lines. In cell proliferation experiments, we found that genistein and biochanin A inhibited SCC15 and SCC25 cell growth with an IC50 of 50 μM. We also investigated the effect of isoflavones on ERK and Akt pathways. Our results, from western blot analysis, suggest that both genistein and biochanin A induced decreases in phosphorylation of ERK and Akt at treatment concentrations of 20, 50 and 100 μM. Taken together, our results clearly demonstrate a differential regulation of signaling pathways by various isoflavones in OSCC cell lines. Thus, tumor progression models can be utilized to study the preventive and therapeutic roles of isoflavones in oral cancer cell lines.

scholarly journals ID:2027 Deregulated expression of key components of phosphoinositide 3 kinase pathway in oral squamous cell carcinoma

2017 ◽  
Vol 4 (S) ◽  
pp. 59
Author(s):  
Satya N Das ◽  
Manasi Mittal ◽  
Manoj K Singh ◽  
Suresh C Sharma
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Cancer ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Squamous Cell ◽  
Pi3k Pathway ◽  
Strong Positive Correlation ◽  
Pi3k Inhibitors ◽  
Cancer Tissues

Oral squamous cell carcinoma (OSCC) is sixth common cancer in males globally. Deregulation of phosphatidylinositol-3-kinase (PI3K) pathway leads to various intracellular responses such as proliferation, survival, and inhibition of apoptosis. We evaluated the expression of key components of PI3K pathway in OSCC patients. RT-PCR and qRT-PCR was used asses the expression of different AKT isoforms, PTEN, TSC1 and TSC2 in tumor and normal tissues. The expression of various components of PI3K pathway e.g.Ser473pAKT, pan-AKT, PTEN and Ser2448pmTOR and mTOR was evaluated by western blot assay. Effect of selected PI3K inhibitors on OSCC cells (SCC-4, SCC-9 and SCC-25) was also studied. Approximately 1.4-fold higher expression of AKT1 and downregulation of AKT2 and AKT3 mRNA was observed in tumor tissue sections of patients as compared to controls. PTEN, TSC1 and TSC2 mRNA was found to be marginally decreases in tumor than the normal area. Significantly strong immunostaining of ser473p-AKT in comparison to AKT1 was documented in all paraffin fixed oral cancer tissues. Additionally, a strong positive correlation between the immuno-histochemical expression of AKT-1 and ser473p-AKT in the paraffin sections of oral cancer tissues was observed (r= 0.7504; p≤0.0001). Aberrant expression of key components of PI3K pathway was also found in OSCC cells that were reversed with the treatment of its inhibitors. Overall, our study suggests that PI3K pathway is deregulated OSCC patients and OSCC cell lines, with AKT1 being the predominantly expressed isoform. PI3K inhibitors restored such aberrations in OSCC cell lines.

A concerted cell and serum proteomic approach for the identification of oral squamous cell carcinoma biomarkers

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5512-5512
Author(s):  
A. M. Mlynarek ◽  
R. Balys ◽  
S. Jie ◽  
Y. Xu ◽  
M. P. Hier ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Cancer ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Squamous Cell ◽  
Serum Biomarkers ◽  
Mouse Serum ◽  
Proteomic Approach ◽  
Albumin Depletion

5512 Background: Head and neck squamous cell carcinoma is the sixth most common cause of cancer deaths in the world. Despite extensive research, the 5-year survival rates have not changed significantly over the last decade. Presently, the lack of serum biomarkers for head and neck carcinoma limits early diagnosis and treatment monitoring of advanced disease. In this study, we used a proteomic approach on serum from mice bearing human oral squamous cell carcinoma xenografts and from conditioned cell culture medium from matched cell lines. Methods: Oral squamous cell carcinomas, with distinct invasive phenotypes, and adjacent normal tissue were obtained from human patients, and were transplanted orthotopicaly into tongues of RAG-2/γ(c) mice. After a 20% weight loss, the mice were sacrificed by exsanguinations. Two distinct proteomic protocols were used to analyze the mouse serum. The first involved albumin depletion followed by two-dimensional gel electrophoresis and MALDI. The second arm utilized the same albumin depletion followed by multidimensional-protein-information-technology (ESI-LC and MS/MS). The top candidate proteins, which were differentially expressed in the cancer bearing mice compared to matched controls were then validated by Western blot, immunoprecipitation, immunofluorescence, and/or immunohistochemistry analyses using mouse serum and conditioned medium from matched cell lines. Results: Orthotopic implantation of human tumor tissues in mouse tongue was successful in 100% of the mice tested. The human origin of these tumors was confirmed pathologically. A correlation between disease stages and invasiveness was observed. We identified over one hundred proteins as being differentially expressed between control and cancer-bearing mice (p < 0.05), including proteins involved in cell cytoskeleton signaling. The expression of these proteins was then validated in mouse serum, tissue xenografts, and conditioned medium from oral cancer matched established cell lines. Conclusion: We report the first proteomic in-vivo model of oral cancer for the identification of low molecular weight serum biomarkers. We identified candidates that can be exploited as potential markers for diagnosis of human oral squamous cell carcinoma. No significant financial relationships to disclose.

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