scholarly journals Genome-wide CRISPR screens of oral squamous cell carcinoma reveal fitness genes in the Hippo pathway

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Annie Wai Yeeng Chai ◽  
Pei San Yee ◽  
Stacey Price ◽  
Shi Mun Yee ◽  
Hui Mei Lee ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Hippo Pathway ◽  
Therapeutic Targets ◽  
Cancer Genes ◽  
Genome Wide ◽  
Therapeutic Value ◽  
The Hippo Pathway

New therapeutic targets for oral squamous cell carcinoma (OSCC) are urgently needed. We conducted genome-wide CRISPR-Cas9 screens in 21 OSCC cell lines, primarily derived from Asians, to identify genetic vulnerabilities that can be explored as therapeutic targets. We identify known and novel fitness genes and demonstrate that many previously identified OSCC-related cancer genes are non-essential and could have limited therapeutic value, while other fitness genes warrant further investigation for their potential as therapeutic targets. We validate a distinctive dependency on YAP1 and WWTR1 of the Hippo pathway, where the lost-of-fitness effect of one paralog can be compensated only in a subset of lines. We also discover that OSCCs with WWTR1 dependency signature are significantly associated with biomarkers of favorable response toward immunotherapy. In summary, we have delineated the genetic vulnerabilities of OSCC, enabling the prioritization of therapeutic targets for further exploration, including the targeting of YAP1 and WWTR1.

scholarly journals The Hippo pathway transcriptional co-activator, YAP, confers resistance to cisplatin in human oral squamous cell carcinoma

2015 ◽  
Vol 46 (6) ◽  
pp. 2364-2370 ◽  
Author(s):  
KYOHEI YOSHIKAWA ◽  
KAZUMA NOGUCHI ◽  
YOSHIRO NAKANO ◽  
MICHIYO YAMAMURA ◽  
KAZUKI TAKAOKA ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Hippo Pathway ◽  
The Hippo Pathway

scholarly journals Genome wide profiling in oral squamous cell carcinoma identifies a four genetic marker signature of prognostic significance

PLoS ONE ◽  
2017 ◽  
Vol 12 (4) ◽  
pp. e0174865 ◽  
Author(s):  
Vui King Vincent-Chong ◽  
Iman Salahshourifar ◽  
Kar Mun Woo ◽  
Arif Anwar ◽  
Rozaimi Razali ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Genetic Marker ◽  
Squamous Cell ◽  
Prognostic Significance ◽  
Genome Wide

scholarly journals Dissecting the Proton Transport Pathway in Oral Squamous Cell Carcinoma: State of the Art and Theranostics Implications

2019 ◽  
Vol 20 (17) ◽  
pp. 4222 ◽  
Author(s):  
Alejandro I. Lorenzo-Pouso ◽  
Mario Pérez-Sayáns ◽  
Samuel Rodríguez-Zorrilla ◽  
Cintia Chamorro-Petronacci ◽  
Abel García-García
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Therapeutic Targets ◽  
Cancer Therapies ◽  
Carbonic Anhydrases ◽  
Transport Pathway ◽  
Diagnosis And Prognosis ◽  
Vacuolar Atpases

Cancer cells overexpress proton exchangers at the plasma membrane in order acidify the extracellular matrix and maintain the optimal pH for sustaining cancer growth. Among the families of proton exchangers implicated in carcinogenesis, carbonic anhydrases (CAs), monocarboxylate transporters (MCTs), Na+/H+ exchangers (NHEs), sodium bicarbonate cotransporters (NBCs), and vacuolar ATPases (V-ATPases) are highlighted. Considerable research has been carried out into the utility of the understanding of these machineries in the diagnosis and prognosis of several solid tumors. In addition, as therapeutic targets, the interference of their functions has contributed to the discovery or optimization of cancer therapies. According to recent reports, the study of these mechanisms seems promising in the particular case of oral squamous cell carcinoma (OSCC). In the present review, the latest advances in these fields are summarized, in particular, the usefulness of proton exchangers as potential prognostic biomarkers and therapeutic targets in OSCC.

scholarly journals Pro-inflammatory Genes as Biomarkers and Therapeutic Targets in Oral Squamous Cell Carcinoma

2010 ◽  
Vol 285 (42) ◽  
pp. 32512-32521 ◽  
Author(s):  
Shailaja K. Rao ◽  
Zoran Pavicevic ◽  
Ziyun Du ◽  
Jong-Gwan Kim ◽  
Meiyun Fan ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Therapeutic Targets ◽  
Inflammatory Genes

Cancer genes alterations and HPV infection in oral squamous cell carcinoma

2010 ◽  
Vol 39 (9) ◽  
pp. 909-915 ◽  
Author(s):  
Branka Popović ◽  
Biljana Jekić ◽  
Ivana Novaković ◽  
Ljiljana Luković ◽  
Vitomir Konstantinović ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Hpv Infection ◽  
Cancer Genes

scholarly journals Integrative Multi−Omics Analysis Reveals Candidate Biomarkers for Oral Squamous Cell Carcinoma

2022 ◽  
Vol 11 ◽  
Author(s):  
Zhengqing Wan ◽  
Haofeng Xiong ◽  
Xian Tan ◽  
Tong Su ◽  
Kun Xia ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Differentially Expressed Genes ◽  
Squamous Cell ◽  
Therapeutic Targets ◽  
Differentially Expressed ◽  
Integrative Approach ◽  
Hub Genes ◽  
Ppi Networks

Oral squamous cell carcinoma (OSCC) is one of the most common types of cancer worldwide. Due to the lack of early detection and treatment, the survival rate of OSCC remains poor and the incidence of OSCC has not decreased during the past decades. To explore potential biomarkers and therapeutic targets for OSCC, we analyzed differentially expressed genes (DEGs) associated with OSCC using RNA sequencing technology. Methylation−regulated and differentially expressed genes (MeDEGs) of OSCC were further identified via an integrative approach by examining publicly available methylomic datasets together with our transcriptomic data. Protein−protein interaction (PPI) networks of MeDEGs were constructed and highly connected hub MeDEGs were identified from these PPI networks. Subsequently, expression and survival analyses of hub genes were performed using The Cancer Genome Atlas (TCGA) database and the Gene Expression Profiling Interactive Analysis (GEPIA) online tool. A total of 56 upregulated MeDEGs and 170 downregulated MeDEGs were identified in OSCC. Eleven hub genes with high degree of connectivity were picked out from the PPI networks constructed by those MeDEGs. Among them, the expression level of four hub genes (CTLA4, CDSN, ACTN2, and MYH11) were found to be significantly changed in the head and neck squamous carcinoma (HNSC) patients. Three hypomethylated hub genes (CTLA4, GPR29, and TNFSF11) and one hypermethylated hub gene (ISL1) were found to be significantly associated with overall survival (OS) of HNSC patients. Therefore, these hub genes may serve as potential DNA methylation biomarkers and therapeutic targets of OSCC.

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