Production of bone-resorbing activity and colony-stimulating activity in vivo and in vitro by a human squamous cell carcinoma associated with hypercalcemia and leukocytosis.

ObjectiveOesophageal squamous cell carcinoma (OSCC), like other squamous carcinomas, harbour highly recurrent cell cycle pathway alterations, especially hyperactivation of the CCND1/CDK4/6 axis, raising the potential for use of existing CDK4/6 inhibitors in these cancers. Although CDK4/6 inhibition has shown striking success when combined with endocrine therapy in oestrogen receptor positive breast cancer, CDK4/6 inhibitor palbociclib monotherapy has not revealed evidence of efficacy to date in OSCC clinical studies. Herein, we sought to elucidate the identification of key dependencies in OSCC as a foundation for the selection of targets whose blockade could be combined with CDK4/6 inhibition.DesignWe combined large-scale genomic dependency and pharmaceutical screening datasets with preclinical cell line models, to identified potential combination therapies in squamous cell cancer.ResultsWe identified sensitivity to inhibitors to the ERBB family of receptor kinases, results clearly extending beyond the previously described minority of tumours with EGFR amplification/dependence, specifically finding a subset of OSCCs with dual dependence on ERBB3 and ERBB2. Subsequently. we demonstrated marked efficacy of combined pan-ERBB and CDK4/6 inhibition in vitro and in vivo. Furthermore, we demonstrated that squamous lineage transcription factor KLF5 facilitated activation of ERBBs in OSCC.ConclusionThese results provide clear rationale for development of combined ERBB and CDK4/6 inhibition in these cancers and raises the potential for KLF5 expression as a candidate biomarker to guide the use of these agents. These data suggested that by combining existing Food and Drug Administration (FDA)-approved agents, we have the capacity to improve therapy for OSCC and other squamous cancer.

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JOSD1 promotes proliferation and chemoresistance of head and neck squamous cell carcinoma under the epigenetic regulation of BRD4

Cancer Cell International ◽

10.1186/s12935-021-02060-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Chao Jing ◽

Dandan Liu ◽

Qingchuan Lai ◽

Linqi Li ◽

Mengqian Zhou ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Gene Expression Omnibus ◽

Neck Squamous Cell Carcinoma ◽

The Cancer Genome Atlas ◽

In Vivo Experiments

Abstract Background Deubiquitinating enzymes (DUBs) play critical roles in various cancers by modulating functional proteins post-translationally. Previous studies have demonstrated that DUB Josephin Domain Containing 1 (JOSD1) is implicated in tumor progression, however, the role and mechanism of JOSD1 in head and neck squamous cell carcinoma (HNSCC) remain to be explored. In this study, we aimed to identify the clinical significance and function of JOSD1 in HNSCC. Methods The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were analyzed to find novel DUBs in HNSCC. Immunohistochemistry assay was performed to determine the expression of JOSD1 in our cohort of 42 patients suffered with HNSCC. Kaplan–Meier analysis was used to identify the correlation between JOSD1 and the prognosis of HNSCC patients. The regulation of BRD4 on JOSD1 was determined by using pharmacological inhibition and gene depletion. The in vitro and in vivo experiments were conducted to elucidate the role of JOSD1 in HNSCC. Results The results of IHC showed that JOSD1 was aberrantly expressed in HNSCC specimens, especially in the chemoresistant ones. The overexpression of JOSD1 indicated poor clinical outcome of HNSCC patients. Moreover, JOSD1 depletion dramatically impaired cell proliferation and colony formation, and promoted cisplatin-induced apoptosis of HNSCC cells in vitro. Additionally, JOSD1 suppression inhibited the tumor growth and improved chemosensitivity in vivo. The epigenetic regulator BRD4 contributed to the upregulation of JOSD1 in HNSCC. Conclusions These results demonstrate that JOSD1 functions as an oncogene in HNSCC progression, and provide a promising target for clinical diagnosis and therapy of HNSCC.

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Cirsiliol targets tyrosine kinase 2 to inhibit esophageal squamous cell carcinoma growth in vitro and in vivo

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-021-01903-z ◽

2021 ◽

Vol 40 (1) ◽

Author(s):

Xuechao Jia ◽

Chuntian Huang ◽

Yamei Hu ◽

Qiong Wu ◽

Fangfang Liu ◽

...

Keyword(s):

Cell Proliferation ◽

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Tumor Model ◽

Kinase Assay ◽

Tyrosine Kinase 2

Abstract Background Esophageal squamous cell carcinoma (ESCC) is an aggressive and lethal cancer with a low 5 year survival rate. Identification of new therapeutic targets and its inhibitors remain essential for ESCC prevention and treatment. Methods TYK2 protein levels were checked by immunohistochemistry. The function of TYK2 in cell proliferation was investigated by MTT [(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] and anchorage-independent cell growth. Computer docking, pull-down assay, surface plasmon resonance, and kinase assay were used to confirm the binding and inhibition of TYK2 by cirsiliol. Cell proliferation, western blot and patient-derived xenograft tumor model were used to determine the inhibitory effects and mechanism of cirsiliol in ESCC. Results TYK2 was overexpressed and served as an oncogene in ESCC. Cirsiliol could bind with TYK2 and inhibit its activity, thereby decreasing dimer formation and nucleus localization of signal transducer and activator of transcription 3 (STAT3). Cirsiliol could inhibit ESCC growth in vitro and in vivo. Conclusions TYK2 is a potential target in ESCC, and cirsiliol could inhibit ESCC by suppression of TYK2.

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Effects of lentivirus-mediated shRNA targeting integrin-linked kinase on oral squamous cell carcinoma in vitro and in vivo

Oncology Reports ◽

10.3892/or.2015.4374 ◽

2015 ◽

Vol 35 (1) ◽

pp. 89-98 ◽

Cited By ~ 5

Author(s):

LIN QUE ◽

DAN ZHAO ◽

XIU-FA TANG ◽

JI-YUAN LIU ◽

XIANG-YU ZHANG ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Integrin Linked Kinase

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Synergetic Effects of PARP Inhibitor AZD2281 and Cisplatin in Oral Squamous Cell Carcinoma in Vitro and in Vivo

International Journal of Molecular Sciences ◽

10.3390/ijms17030272 ◽

2016 ◽

Vol 17 (3) ◽

pp. 272 ◽

Cited By ~ 13

Author(s):

Masaaki Yasukawa ◽

Hisako Fujihara ◽

Hiroaki Fujimori ◽

Koji Kawaguchi ◽

Hiroyuki Yamada ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Parp Inhibitor ◽

Synergetic Effects

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CXCL6 fuels the growth and metastases of esophageal squamous cell carcinoma cells both in vitro and in vivo through upregulation of PD‐L1 via activation of STAT3 pathway

Journal of Cellular Physiology ◽

10.1002/jcp.30236 ◽

2020 ◽

Author(s):

Shutao Zheng ◽

Tongxue Shen ◽

Qing Liu ◽

Tao Liu ◽

Aerziguli Tuerxun ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Carcinoma Cells ◽

Stat3 Pathway

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The molecular mechanisms of the long noncoding RNA SBF2-AS1 in regulating the proliferation of oesophageal squamous cell carcinoma

Scientific Reports ◽

10.1038/s41598-020-80817-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Wenjuan Zha ◽

Xiaomin Li ◽

Xiaowei Tie ◽

Yao Xing ◽

Hao Li ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Noncoding Rna ◽

Molecular Mechanisms ◽

Histological Grade ◽

Oesophageal Squamous Cell Carcinoma ◽

Lymphnode Metastasis

AbstractThe long noncoding RNASBF2-AS1 can promote the occurrence and development of many kinds of tumours, but its role in oesophageal squamous cell carcinoma (ESCC) is unknown. We found that SBF2-AS1 was up-regulated in ESCC, and its expression was positively correlated with tumor size (P = 0.0001), but was not related to gender, age, TNM stage, histological grade, and lymphnode metastasis (P > 0.05). It was further found that the higher the expression of SBF2-AS1, the lower the survival rate. COX multivariate analysis showed that the expression of SBF2-AS1 was an independent prognostic factor. Functional experiments show that inhibition of SBF2-AS1 can inhibit the proliferation of ESCC through in vivo and in vitro, and overexpression of SBF2-AS1 can promote the proliferation of ESCC and inhibit its apoptosis. In mechanism, SBF2-AS1/miR-338-3P, miR-362-3P/E2F1 axis are involved in the regulation of ESCC growth. In general, SBF2-AS1 may be used as ceRNA to combine with miR-338-3P and miR-362-3P to up-regulate the expression ofE2F1, and ultimately play a role in promoting cancer. It may be used as a therapeutic target and a biomarker for prognosis.

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