Targeting Notch and EGFR signaling in human mucoepidermoid carcinoma

Ni, Wei; Chen, Zirong; Zhou, Xin; Yang, Ruiqi; Mu, Yu; Lu, Jianrong; Kaye, Frederic J.; Wu, Lizi

doi:10.1038/s41392-020-00388-0

Cited by 17 publications

(16 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…DBZ interferes with Notch receptor processing, preventing the release of the intracellular domain of Notch from the cell membrane and blocking the transcriptional activation of Notch target genes. 33 We treated Caki-2 cells with 1 μM DBZ for 72 h and observed a reduction of HES1 by western blot analysis, confirming that DBZ inhibited Notch signaling (Figure 5D). Moreover, the data showed that the DBZ inhibited Caki-2 cells growth (Figure 5E) and invasion/migration (Figure 5F) in vitro.…”

Section: Pathway Analysis Of Brd9 In Negative Hif-2α Ccrccsupporting

confidence: 60%

Bromodomain‐containing protein 9 is a prognostic biomarker associated with immune infiltrates and promotes tumor malignancy through activating notch signaling pathway in negative HIF‐2α clear cell renal cell carcinoma

Lou

Gao

et al. 2021

IUBMB Life

View full text Add to dashboard Cite

HIF-2α selective inhibitor showed successful efficacy in sensitive clear cell renal cell carcinoma (ccRCC) presenting higher levels of HIF-2α compared to resistant tumors with low level of HIF-2α (negative HIF-2α ccRCC). Currently, negative HIF-2α ccRCC lacks truly effective therapeutic agents to improve the outcomes. Bromodomain-containing protein 9 (BRD9) plays a critical role in human hepatocellular carcinoma, squamous cell lung cancer, acute myeloid leukemia, and so on. However, expression and biological role of BRD9 in negative HIF-2α ccRCC is poorly understood. Clinically, we demonstrated that expression of BRD9 in negative HIF-2α ccRCC tissues was higher than that in positive HIF-2α ccRCC. Moreover, high BRD9 expression was correlated with unfavorable clinicopathological features and predicted the poor overall survival of negative HIF-2α ccRCC patients. Functionally, BRD9 knockout resulted in reduced proliferation, migration and invasion of negative HIF-2α ccRCC cells (Caki-2). In addition, BRD9 was related to the TIIC infiltration level in negative HIF-2α ccRCC tissues. Mechanistically, Gene set enrichment analysis (GSEA) showed that BRD9 was closely related to Notch signaling pathway. BRD9 knockout resulted in reduced mRNA level of Hes1 and Notch1 in negative HIF-2α ccRCC in vitro. The overexpression of NICD (Notch intracellular domain) enhanced malignant behaviors of Caki-2 cells with BRD9 knockout. And Notch inhibition led to attenuation of cell growth and reduced migration and invasion in Caki-2 cells. Overall, our results identified that BRD9 promotes the proliferation, migration and invasion of negative HIF-2α ccRCC cells by targeting Notch signaling pathway and serve as a promising biomarker for negative HIF-2α ccRCC.

show abstract

Section: Pathway Analysis Of Brd9 In Negative Hif-2α Ccrccsupporting

confidence: 60%

Bromodomain‐containing protein 9 is a prognostic biomarker associated with immune infiltrates and promotes tumor malignancy through activating notch signaling pathway in negative HIF‐2α clear cell renal cell carcinoma

Lou

Gao

et al. 2021

IUBMB Life

View full text Add to dashboard Cite

show abstract

“…Interestingly, a study in liver cancer model showed that tumor cells that failed at H3K9Ac/H3K9Me3 transition, could lead to the hyperacetylation of H3K9 and increased expression of many oncogenes such as Kras, Ercc1, Cdk6, Usp39, and Mapre3 52 . In addition, previous studies reported that levels of H3K9Ac and H3K18Ac were correlated with the increased transcription of genes, which could be involved in salivary gland carcinogenesis, such as NOTCH1 (both H3K9Ac and H3K18Ac) 53,54 , MUC1 (H3K9Ac) 55 , c-MYB (H3K9Ac) 56 and EGFR downstream protein (H3K18Ac) 54,[57][58][59] . Moreover, the MECT1-MAML2, fusion oncogene commonly detected in MEC 60 , was shown to recruit and activate activity of CBP/p300, which is an H3K18 acetyltransferase 61,62 .…”

Section: Discussionmentioning

confidence: 98%

Distinct histone H3 modification profiles correlate with aggressive characteristics of salivary gland neoplasms

Lam‐ubol

Phattarataratip

2022

Sci Rep

View full text Add to dashboard Cite

Post-translational modification of histones is the crucial event that affect many tumor-specific traits. A diverse type of histone modifications had been reported in different cancers with prognostic implications. This study aimed to examine the degree of histone H3 modifications in salivary gland neoplasms and their associations with tumor pathologic characteristics and proliferative activity. The expression of H3K9Ac, H3K18Ac, H3K9Me3 and Ki-67 in 70 specimens of salivary gland neoplasms, consisting of 30 mucoepidermoid carcinoma (MEC), 20 adenoid cystic carcinoma (ACC) and 20 pleomorphic adenoma (PA), were investigated immunohistochemically. The immunohistochemical scoring of 3 histone modification types and Ki-67 labeling index were determined. Overall, MEC demonstrated elevated H3K9Ac level compared with benign PA. Increased H3K9Me3 in MEC was positively correlated with small nest invasion at tumor front, advanced pathologic grade, and elevated proliferative index. In addition, the significant upregulation of all 3 types of histone H3 modification was noted in solid subtype of ACC and associated with increased cell proliferation. This study indicates that salivary gland neoplasms differentially acquire distinct patterns of histone H3 modification, which impact prognostically relevant cancer phenotypes. The hyperacetylation and methylation of histone H3 could be underpinning the prognostically worsen solid type of ACC, and the trimethylation of H3K9 may be involved in aggressive characteristics of MEC.

show abstract

“…MEC tumorigenesis is related to abnormal EGFR signaling [ 15 , 16 , 28 ]. Cetuximab inhibits MEC cell proliferation by blocking EGFR.…”

Section: Discussionmentioning

confidence: 99%

Establishment of Mucoepidermoid Carcinoma Cell Lines from Surgical and Recurrence Biopsy Specimens

Yamanaka

Suzuki²,

Ito³

et al. 2023

IJMS

View full text Add to dashboard Cite

Patients with advanced/recurrent mucoepidermoid carcinoma (MEC) have a poor prognosis. This study aimed to establish and characterize human mucoepidermoid carcinoma cell lines from the initial surgical specimen and biopsy specimen upon recurrence from the same patient to provide a resource for MEC research. MEC specimens from the initial surgical procedure and biopsy upon recurrence were used to establish cell lines. The established cell lines were cytogenetically characterized using multi-color fluorescence in situ hybridization and detection, and the sequence of the CRTC1-MAML2 chimeric gene was determined. Furthermore, the susceptibility of head and neck mucoepidermoid carcinoma to standard treatment drugs such as cisplatin, 5-fluorouracil, and cetuximab was investigated. We successfully established unique MEC cell lines, AMU-MEC1, from an initial surgical specimen and AMU-MEC1-R1 and AMU-MEC1-R2 from the recurrent biopsy specimen in the same patient. These cell lines exhibited epithelial morphology and developed in vitro-like cobblestones. They shared eight chromosomal abnormalities, including der(19)ins(19;11)(p13;?), which resulted in a chimeric CRTC1-MAML2 gene, indicating the same origin of the cell lines. The susceptibility of all cell lines to cisplatin and 5-fluorouracil was low. Interestingly, EGFR dependency for cell growth decreased in AMU-MEC-R1 and AMU-MEC-R2 but was retained in AMU-MEC1. These cytogenetic and biochemical findings suggest that the established cell lines can be used to investigate the disease progression mechanisms and develop novel therapeutics for MEC.

show abstract

Targeting Notch and EGFR signaling in human mucoepidermoid carcinoma

Cited by 17 publications

References 56 publications

Bromodomain‐containing protein 9 is a prognostic biomarker associated with immune infiltrates and promotes tumor malignancy through activating notch signaling pathway in negative HIF‐2α clear cell renal cell carcinoma

Bromodomain‐containing protein 9 is a prognostic biomarker associated with immune infiltrates and promotes tumor malignancy through activating notch signaling pathway in negative HIF‐2α clear cell renal cell carcinoma

Distinct histone H3 modification profiles correlate with aggressive characteristics of salivary gland neoplasms

Establishment of Mucoepidermoid Carcinoma Cell Lines from Surgical and Recurrence Biopsy Specimens

Contact Info

Product

Resources

About