SATB1 as oncogenic driver and potential therapeutic target in head &amp; neck squamous cell carcinoma (HNSCC)

Panchal, Omkar; Wichmann, Gunnar; Grénman, Reidar; Eckhardt, Lisa; Kunz‐Schughart, Leoni A.; Franke, Heike; Dietz, Andreas; Aigner, Achim

doi:10.1038/s41598-020-65077-y

Cited by 9 publications

(3 citation statements)

References 43 publications

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“…erapies currently approved by the FDA for the treatment of advanced metastatic head and neck cancer include cetuximab, an antibody that blocks the receptor tyrosine kinase (RTK) epithelial growth factor receptor (EGFR), and it is usually combined with other radiotherapy drugs for the treatment of advanced locally metastatic head and neck cancer [3,4]. Although cetuximab can significantly prolong the median overall survival of head and neck cancer patients, the clinical remission rate was limited to late local disease with a course of about 10 months or metastatic disease with a course of 2-3 months [5][6][7][8]. Head and neck cancer patients were resistant to cetuximab since they received cetuximab, while a latest clinical study on patients receiving cetuximab monotherapy found that 87% of head and neck cancer patients had resistance to cetuximab since they received cetuximab, while the remaining 13% of patients responded to cetuximab sensitively at the beginning, but it has acquired drug resistance with the extension of the clinical application time of the drug.…”

Section: Introductionmentioning

confidence: 99%

FOXD1 Regulates the Sensitivity of Cetuximab by Regulating the Expression of EGFR in Head and Neck Squamous Cell Cancer

Zhang

et al. 2022

Journal of Healthcare Engineering

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Objectives. Previous experiments have shown that growth factor receptors play important role in tumor proliferation, metastasis, and therapeutic effect of chemotherapeutic drugs. At the same time, forkhead box D1 (FOXD1) plays an important role in a variety of signal transmission, but its expression profile was known little about head and neck cancer. The purpose of this experiment was to explore the regulation of FOXD1 on the tumor progression of head and neck cancer and to explore the correlation of FOXD1 on the expression of growth factor receptors (EGFR). Methods. The bioinformatics online database analyzed the expression of FOXD1 and EGFR in tumor tissues and nontumor tissues. Real-time quantitative PCR was used to detect the FOXD1 and EGFR expression in 45 tumor tissues and 15 nontumor tissues. The plasmid was used to construct FOXD1 overexpressing head and neck squamous cell cancer lines and observe the clonal formation and invasion of tumor cells under the intervention of EGFR-specific antibody—cetuximab. Results. The expression of FOXD1 and EGFR in tumor tissues was higher than that in nontumor tissues. The higher expression of FOXD1 and EGFR was not conducive to the prognosis of patients. The expression of FOXD1 and EGFR was positively correlated, and immunohistochemical analysis showed the high expression of FOXD1 and EGFR has close relation to the advanced stage of the tumor. In vitro cell experiments proved that overexpression of FOXD1 can partially offset the cloning ability of cetuximab on head and neck tumor cells. Conclusion. FOXD1 has an important regulatory role in the progression of head and neck cancer, and its abnormally high expression was not conducive to the prognosis of cancer patients. FOXD1 can regulate the expression of growth factor receptors in head and neck cancer, which provides a new idea for the better use of tumor growth factor receptor-specific antibodies for collaborative therapy.

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Section: Introductionmentioning

confidence: 99%

FOXD1 Regulates the Sensitivity of Cetuximab by Regulating the Expression of EGFR in Head and Neck Squamous Cell Cancer

Zhang

et al. 2022

Journal of Healthcare Engineering

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“…High SATB1 expression is related to HNSCC metastasis, poor prognosis, and decreased survival rate. 241 The zinc finger and SCAN domain containing 4 (ZSCAN4) is another example of a protein that can alter the epigenetic profile and chromatin state in tumors. 242 ZSCAN4 induces the functional hyperacetylation of histone 3 at the OCT3/4 and NANOG promoters, thereby upregulating CSC factors.…”

Section: Epigenetic Modifications Promote the Development Of Osccmentioning

confidence: 99%

Oral squamous cell carcinomas: state of the field and emerging directions

Tan,

Wang,

et al. 2023

Int J Oral Sci

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Oral squamous cell carcinoma (OSCC) develops on the mucosal epithelium of the oral cavity. It accounts for approximately 90% of oral malignancies and impairs appearance, pronunciation, swallowing, and flavor perception. In 2020, 377,713 OSCC cases were reported globally. According to the Global Cancer Observatory (GCO), the incidence of OSCC will rise by approximately 40% by 2040, accompanied by a growth in mortality. Persistent exposure to various risk factors, including tobacco, alcohol, betel quid (BQ), and human papillomavirus (HPV), will lead to the development of oral potentially malignant disorders (OPMDs), which are oral mucosal lesions with an increased risk of developing into OSCC. Complex and multifactorial, the oncogenesis process involves genetic alteration, epigenetic modification, and a dysregulated tumor microenvironment. Although various therapeutic interventions, such as chemotherapy, radiation, immunotherapy, and nanomedicine, have been proposed to prevent or treat OSCC and OPMDs, understanding the mechanism of malignancies will facilitate the identification of therapeutic and prognostic factors, thereby improving the efficacy of treatment for OSCC patients. This review summarizes the mechanisms involved in OSCC. Moreover, the current therapeutic interventions and prognostic methods for OSCC and OPMDs are discussed to facilitate comprehension and provide several prospective outlooks for the fields.

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“…One example of a genome-organizing protein is special AT-rich sequence binding protein 1 (SATB1), which can modify the structure of chromatin and direct chromatin remodeling enzymes to specific regions to regulate gene expression. Increased levels of SATB1 expression have been linked with metastasis, poor prognosis, and decreased survival rates [395] in head and neck squamous cell carcinoma (HNSCC) [396].…”

Section: Histone Modifications In Osccmentioning

confidence: 99%

Epigenetic Regulation in Oral Squamous Cell Carcinoma Microenvironment: A Comprehensive Review

Mesgari,

Esmaelian,

Nasiri

et al. 2023

Cancers

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Oral squamous cell carcinoma (OSCC) is a prevalent and significant type of oral cancer that has far-reaching health implications worldwide. Epigenetics, a field focused on studying heritable changes in gene expression without modifying DNA sequence, plays a pivotal role in OSCC. Epigenetic changes, encompassing DNA methylation, histone modifications, and miRNAs, exert control over gene activity and cellular characteristics. In OSCC, aberrant DNA methylation of tumor suppressor genes (TSG) leads to their inactivation, subsequently facilitating tumor growth. As a result, distinct patterns of gene methylation hold promise as valuable biomarkers for the detection of OSCC. Oral cancer treatment typically involves surgery, radiation therapy, and chemotherapy, but even with these treatments, cancer cells cannot be effectively targeted and destroyed. Researchers are therefore exploring new methods to target and eliminate cancer cells. One promising approach is the use of epigenetic modifiers, such as DNA methyltransferase (DNMT) inhibitors and histone deacetylase (HDAC) inhibitors, which have been shown to modify abnormal epigenetic patterns in OSCC cells, leading to the reactivation of TSGs and the suppression of oncogenes. As a result, epigenetic-targeted therapies have the potential to directly alter gene expression and minimize side effects. Several studies have explored the efficacy of such therapies in the treatment of OSCC. Although studies have investigated the efficacy of epigenetic therapies, challenges in identifying reliable biomarkers and developing effective combination treatments are acknowledged. Of note, epigenetic mechanisms play a significant role in drug resistance in OSCC and other cancers. Aberrant DNA methylation can silence tumor suppressor genes, while alterations in histone modifications and chromatin remodeling affect gene expression related to drug metabolism and cell survival. Thus, understanding and targeting these epigenetic processes offer potential strategies to overcome drug resistance and improve the efficacy of cancer treatments in OSCC. This comprehensive review focuses on the complex interplay between epigenetic alterations and OSCC cells. This will involve a deep dive into the mechanisms underlying epigenetic modifications and their impact on OSCC, including its initiation, progression, and metastasis. Furthermore, this review will present the role of epigenetics in the treatment and diagnosis of OSCC.

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SATB1 as oncogenic driver and potential therapeutic target in head & neck squamous cell carcinoma (HNSCC)

Cited by 9 publications

References 43 publications

FOXD1 Regulates the Sensitivity of Cetuximab by Regulating the Expression of EGFR in Head and Neck Squamous Cell Cancer

FOXD1 Regulates the Sensitivity of Cetuximab by Regulating the Expression of EGFR in Head and Neck Squamous Cell Cancer

Oral squamous cell carcinomas: state of the field and emerging directions

Epigenetic Regulation in Oral Squamous Cell Carcinoma Microenvironment: A Comprehensive Review

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