<scp>AKT</scp>3 drives adenoid cystic carcinoma development in salivary glands

Zboray, Katalin; Mohrherr, Julian; Stiedl, Patricia; Pranz, Klemens; Wandruszka, Laura; Grabner, Beatrice; Eferl, Robert; Moriggl, Richard; Stoiber, Dagmar; Sakamoto, Kazuhiro; Wagner, Kay Uwe; Popper, Helmut; Casanova, Emilio; Moll, Herwig P.

doi:10.1002/cam4.1293

Cited by 13 publications

(8 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is intriguing to note that PI3K/AKT/mTOR pathways would contribute to cancer cell proliferation in head and neck squamous cell carcinoma (HNSCC), possibly serving a pro-tumorigenic function [ 48 ]. In accordance with the above HNSCC study, the most common malignant salivary gland neoplasm, adenoid cystic carcinoma, exhibits similar characteristics in the PI3K/AKT/mTOR axis [ 49 ]. One therapeutic method for tumors was to target the PI3K/AKT/mTOR pathways with an inhibitor [ 50 ].…”

Section: Discussionsupporting

confidence: 53%

Comprehensive analysis of the transcriptome‐wide m6A methylome in invasive malignant pleomorphic adenoma

et al. 2021

View full text Add to dashboard Cite

Background Invasive malignant pleomorphic adenoma (IMPA) is a highly invasive parotid gland tumor and lacks effective therapy. N6-Methyladenosine (m6A) is the most prevalent post-transcriptional modification of mRNAs in eukaryotes and plays an important role in the pathogenesis of multiple tumors. However, the significance of m6A-modified mRNAs in IMPA has not been elucidated to date. Hence, in this study, we attempted to profile the effect of IMPA in terms of m6A methylation in mRNA. Methods Methylated RNA immunoprecipitation with next-generation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq) were utilized to acquire the first transcriptome-wide profiling of the m6A methylome map in IMPA followed by bioinformatics analysis. Results In this study, we obtained m6A methylation maps of IMPA samples and normal adjacent tissues through MeRIP-seq. In total, 25,490 m6A peaks associated with 13,735 genes were detected in the IMPA group, whereas 33,930 m6A peaks associated with 18,063 genes were detected in the control group. Peaks were primarily enriched within coding regions and near stop codons with AAACC and GGAC motifs. Moreover, functional enrichment analysis demonstrated that m6A-containing genes were significantly enriched in cancer and metabolism relevant pathways. Furthermore, we identified a relationship between the m6A methylome and the RNA transcriptome, indicating a mechanism by which m6A modulates gene expression. Conclusions Our study is the first to provide comprehensive and transcriptome-wide profiles to determine the potential roles played by m6A methylation in IMPA. These results may open new avenues for in-depth research elucidating the m6A topology of IMPA and the molecular mechanisms governing the formation and progression of IMPA.

show abstract

Section: Discussionsupporting

confidence: 53%

Comprehensive analysis of the transcriptome‐wide m6A methylome in invasive malignant pleomorphic adenoma

et al. 2021

View full text Add to dashboard Cite

show abstract

“…AKT3 is a homologous gene that belongs to the serine/ threonine protein kinase AKT subfamily. Once AKT3 has been hyperactivated in tumorigenesis, it could be a vulnerable node to be targeted (Zboray, Mohrherr, Stiedl, Pranz, & Wandruszka, 2017). The expression and activation of AKT3 mediates cancer progression and controls cellular processes such as cell growth, proliferation, apoptosis, and invasion (Kim et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‐16 functions as a tumor‐suppressor gene in oral squamous cell carcinoma by targeting AKT3 and BCL2L2

Wang

2018

Journal Cellular Physiology

View full text Add to dashboard Cite

Aberrant expressions of microRNAs have been reported to be strongly associated with the progression and prognosis of various tumors, including oral squamous cell carcinoma (OSCC). Recent studies on miRNA expression profiling have suggested that microRNA‐16 (miR‐16) may be dysregulated in OSCC. However, the tumorigenic roles and mechanisms of miR‐16 in OSCC are still largely unknown. In this study, we demonstrated that miR‐16 was specifically downregulated in both OSCC patients and cancer cell lines. In addition, functional roles of miR‐16 in vitro suggested that the miR‐16 mimic inhibited cell proliferation and induced apoptosis, whereas miR‐16 inhibitor displayed the opposite effects. Luciferase reporter assay and correlation analysis showed that AKT3 and BCL2L2 were directly targeted by miR‐16 and were inversely expressed with miR‐16 in OSCC. Moreover, restoration of AKT3 and BCL2L2 expression could partially reverse the cell proliferation inhibition and apoptosis induction caused by miR‐16. In xenograft nude mice, miR‐16 mimics decreased the expression of AKT3 and BCL2L2 and reduced the tumors volumes and weights, whereas the miR‐16 inhibitor exhibited adverse effects in the derived xenografts. In conclusion, the findings suggested that miR‐16 functions as a tumor suppressor miRNA to inhibit cell proliferation and induce apoptosis in OSCC through decreasing the oncogenes AKT3 and BCL2L2 and that miR‐16 could be a potential therapeutic target for OSCC.

show abstract

“…It has been found that NGF can activate PI3K/AKT pathway through phosphorylating AKT in SACC, thereby potentially stimulating scattering and migration of tumor cells which enhances the progression of PNI (60). Additionally, animal experiments have also shown that a high expression of Akt3 serves as a driving factor of salivary gland tumor progression (43). In addition, the NT-3/TrkC axis promotes the progression of PNI and the poor prognosis of SACC by regulating the interaction between SACC cells and SC.…”

Section: Ngf Family and Receptorsmentioning

confidence: 99%

Perineural Invasion in Adenoid Cystic Carcinoma of the Salivary Glands: Where We Are and Where We Need to Go

et al. 2020

View full text Add to dashboard Cite

Adenoid cystic carcinoma of the salivary gland (SACC) is a rare malignant tumors of the head and neck region, but it is one of the most common malignant tumors that are prone to perineural invasion (PNI) of the head and neck. The prognosis of patients with SACC is strongly associated with the presence of perineural spread (PNS). Although many contributing factors have been reported, the mechanisms underlying the preferential destruction of the blood-nerve barrier (BNB) by tumors and the infiltration of the tumor microenvironment by nerve fibers in SACC, have received little research attention. This review summarizes the current knowledge concerning the characteristics of SACC in relation to the PNI, and then highlights the interplay between components of the tumor microenvironment and perineural niche, as well as their contributions to the PNI. Finally, we provide new insights into the possible mechanisms underlying the pathogenesis of PNI, with particular emphasis on the role of extracellular vesicles that may serve as an attractive entry point in future studies.

show abstract

AKT3 drives adenoid cystic carcinoma development in salivary glands

Cited by 13 publications

References 42 publications

Comprehensive analysis of the transcriptome‐wide m6A methylome in invasive malignant pleomorphic adenoma

Comprehensive analysis of the transcriptome‐wide m6A methylome in invasive malignant pleomorphic adenoma

MicroRNA‐16 functions as a tumor‐suppressor gene in oral squamous cell carcinoma by targeting AKT3 and BCL2L2

Perineural Invasion in Adenoid Cystic Carcinoma of the Salivary Glands: Where We Are and Where We Need to Go

Contact Info

Product

Resources

About