Dual inhibition of autophagy and PI3K/mTOR pathway as a potential therapeutic strategy against laryngeal squamous cell carcinoma

Huang, Huiying; Li, Kenan; Lau, Hui-Ching; Hsueh, Chi‐Yao; Cong, Ning; Zhang, Ming

doi:10.21037/tcr-21-2325

Cited by 7 publications

(3 citation statements)

References 23 publications

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“…Despite substantial improvements in clinical management methods such as radiotherapy, chemotherapy, and surgery, the 5-year overall survival in LSCC has not improved significantly over the past 20 years [ 3 ]. In recent years, new targeted drugs have the hope of improving the prognosis of LSCC patients in the metastatic environment [ 4 ]. Therefore, the unraveling of the pathogenesis of LSCC is urgently needed to identify its diagnostic biomarkers and effective new therapeutic targets.…”

Section: Introductionmentioning

confidence: 99%

ERCC6L facilitates the progression of laryngeal squamous cell carcinoma by the binding of FOXM1 and KIF4A

et al. 2023

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The role of excision repair cross-complementation group 6-like (ERCC6L) has been reported in several cancers, but little is known about its expression and function in laryngeal squamous cell carcinoma (LSCC). In this study, the expression of ERCC6L in LSCC was determined by immunohistochemistry and its correlation with prognostic factors was analyzed. Furthermore, cytological functional validation elucidated the role and underlying mechanisms of ERCC6L dysregulation in LSCC. Our data revealed that ERCC6L expression was elevated in LSCC and it’s correlated with TNM stage. In addition, ERCC6L knockdown LSCC cells showed decreased proliferation and migration, increased apoptosis, and reactive oxygen species (ROS). Mechanically, overexpression of ERCC6L promoted nuclear translocation of FOXM1 to facilitate direct binding to the KIF4A promoter and upregulated KIF4A expression. Furthermore, KIF4A knockdown attenuated the role of ERCC6L overexpression in promoting proliferation, migration, and tumorigenesis of LSCC cells. In summary, ERCC6L promoted the binding of FOXM1 and KIF4A in LSCC cells to drive their progression, which may be a promising target for precision therapy in this disease.

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Section: Introductionmentioning

confidence: 99%

ERCC6L facilitates the progression of laryngeal squamous cell carcinoma by the binding of FOXM1 and KIF4A

et al. 2023

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“… 14 Huang HY et al found that autophagy inhibitors significantly increased LC cell apoptosis and death both in vitro and in vivo . 28 The report of Chen L et al showed that miR-101 lowered the autophagy, proliferation and enhanced the apoptosis in LC cells. 29 In addition, studies have indicated that compared with normal laryngeal tissues, HPV-infected respiratory papilloma tissues have more LC3B expression and autophagosomes.…”

Section: Discussionmentioning

confidence: 99%

NRSN2 promotes the malignant behavior of HPV-transfected laryngeal carcinoma cells through AMPK/ULK1 pathway mediated autophagy activation

Guo,

Wen,

et al. 2024

Cancer Biology & Therapy

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Neurensin-2 (NRSN2) performs a pro-carcinogenic function in multiple cancers. However, the function of NRSN2 in HPV-infected laryngeal carcinoma (LC) remains unclear. HPV transfection was performed in LC cells. The mRNA and protein levels were monitored using RT-qPCR, immunoblotting, and IF. Cell viability and proliferation were found using the CCK-8 assay and Edu staining. Cell invasion, migration, and apoptosis were probed using the Transwell, wound healing, and flow cytometry, respectively. The autophagosome was observed using TEM. NRSN2 was overexpressed in HPV-transfected LC cells. Inhibition of NRSN2 restrained the autophagy and malignant behavior of HPV-transfected LC cells. Meanwhile, the inhibition of AMPK/ULK1 pathway limited the increased autophagy of HPV-transfected LC cells caused by NRSN2 overexpression. Furthermore, NRSN2 knockdown inhibits autophagy by suppressing AMPK/ULK1 pathway, thereby restraining the malignant behavior of HPV-transfected LC cells. Our research confirmed that HPV transfection increased the autophagy and malignant behavior of LC cells by regulating the NRSN2-mediated activation of the AMPK/ULK1 pathway, offering a new target for cure of LC.

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“…Rapamycin binds handiest to at least one mTOR complicated, mTORC1, and inhibits handiest mTORC1-related signaling features 33 . This brought about the invention of ATP-aggressive mTOR inhibitors 34 that bind to each mTORC1 and mTORC2 and inhibit the kinase-based features of mTOR 35 .…”

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confidence: 99%

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2023

IJPSR

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The PI3K-AKT-mTOR signaling pathway is widely used in cancer therapy as it is a signaling pathway that is frequently disrupted in human cancers. Increasingly, inhibitors develop against key proteins in signaling pathways, such as PI3K and mTOR. Dual inhibitors targeting PI3K and mTOR are more potent than one inhibitor targeting only a single protein. This study used to design and molecular docking analysis to investigate the precise binding positions and interaction forces of quinoxaline-containing compounds within the active site of PI3Kγ and mTOR with the help of freely available software for virtual screening of compounds, docking, and drug interaction result analysis. And also proposed the development of new potent drug candidates which works as dual inhibitors against cancer diseases; thus it could be concluded that Quinoxaline-containing derivatives might be used as a template for destiny improvement thru change or derivatization to lay out stronger healing agents. INTRODUCTION:Cancer is an epidemic worldwide, a leading cause of death worldwide, accounting for nearly 10 million deaths in 2020, or nearly one in six deaths. The most common cancers are breast, lung, colon, rectum, and prostate cancers 1 . With the worldwide devastation the sickness is wreaking, the call for brand-new and powerful drugs is inexhaustible. The position of the PI3K-AKT-mTOR signaling pathway is an essential boom signaling pathway, advancing our knowledge that its ongoing activation in numerous cancers kinds is rising as a fascinating goal for most cancers therapy 2-5 .

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Dual inhibition of autophagy and PI3K/mTOR pathway as a potential therapeutic strategy against laryngeal squamous cell carcinoma

Cited by 7 publications

References 23 publications

ERCC6L facilitates the progression of laryngeal squamous cell carcinoma by the binding of FOXM1 and KIF4A

ERCC6L facilitates the progression of laryngeal squamous cell carcinoma by the binding of FOXM1 and KIF4A

NRSN2 promotes the malignant behavior of HPV-transfected laryngeal carcinoma cells through AMPK/ULK1 pathway mediated autophagy activation

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