Prognostic Value of WNT1, NOTCH1, PDGFRβ, and CXCR4 in Oral Squamous Cell Carcinoma

Cierpikowski, Piotr; Lis-Nawara, Anna; Bär, Julia

doi:10.21873/anticanres.16195

Cited by 6 publications

(8 citation statements)

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“…Previous studies have identi ed frequent upregulation and mutations in various WNT family members in diverse cancer types [40]. In addition, an association between the WNT signaling pathway and OSCC prognosis has been established [41][42][43][44][45][46][47][48], positioning it as an independent prognostic factor [16, 49,50]. The role of WNT/β-catenin activation in mediating chemoresistance in other cancers has also been con rmed in the emerging literature [18, 51,52], in which WNT/β-catenin activation supports 5FU-resistance through mechanisms such as cancer stem cell, metastasis, and enhanced transcriptional activity [19,[53][54][55].…”

Section: Discussionmentioning

confidence: 99%

WNT3 promotes chemoresistance to 5-Fluorouracil in oral squamous cell carcinoma via activating the canonical β-catenin pathway

Sun,

Zhang,

Gan

et al. 2024

Preprint

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Objectives 5-Fluorouracil (5FU) is a primary chemotherapeutic agent used to treat oral squamous cell carcinoma (OSCC). However, the development of drug resistance has significantly limited its clinical application. Therefore, there is an urgent need to determine the mechanisms underlying drug resistance and identify effective targets. In recent years, the WNT signaling pathway has been increasingly studied in cancer drug resistance; however, the role of WNT3, a ligand of the canonical WNT signaling pathway, in OSCC drug resistance is not clear. This study delved into this potential connection. Materials and Methods 5FU-resistant cell lines were established by gradually elevating the drug concentration in the culture medium. Differential gene expressions between parental and resistant cells underwent RNA sequencing analysis, which was then substantiated via Real-time quantitative PCR (RT-qPCR) and western blot tests. The influence of the WNT signaling on OSCC chemoresistance was ascertained through WNT3 knockdown or overexpression. The WNT inhibitor methyl 3-benzoate (MSAB) was probed for its capacity to boost 5FU efficacy. Results In this study, by constructing 5FU-resistant OSCC cell lines, the WNT/β-catenin signaling pathway was obviously activated in the drug-resistant cell lines through transcriptome sequencing analysis, RT-qPCR and western blot verification, and the key ligand for activation of the pathway, WNT3, was found. By knocking down WNT3 in resistant cells or overexpressing WNT3 in parental cells, we found that WNT3 promoted 5FU-resistance in OSCC. In addition, the WNT inhibitor MSAB reversed 5FU-resistance in OSCC cells. Conclusions These data underscored the activation of the WNT/β-catenin signaling pathway in resistant cells and identified the promoting effect of WNT3 upregulation on 5FU-resistance in oral squamous carcinoma. This may provide a new therapeutic strategy for reversing 5FU-resistance in OSCC cells. Clinical Relevance The clinical relevance of this study lies in providing a new therapeutic strategy for reversing 5FU-resistance in OSCC.

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Section: Discussionmentioning

confidence: 99%

WNT3 promotes chemoresistance to 5-Fluorouracil in oral squamous cell carcinoma via activating the canonical β-catenin pathway

Sun,

Zhang,

Gan

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Previous studies have identified frequent upregulation and mutations in various WNT family members in diverse cancer types [ 44 ]. In addition, an association between the WNT signaling pathway and OSCC prognosis has been established [ 45 – 52 ], positioning it as an independent prognostic factor [ 16 , 53 , 54 ]. The role of WNT/β-catenin activation in mediating chemoresistance in other cancers has also been confirmed in the emerging literature [ 18 , 55 , 56 ], in which WNT/β-catenin activation supports 5FU-resistance through mechanisms such as cancer stem cell, metastasis, and enhanced transcriptional activity [ 19 , 57 – 59 ].…”

Section: Discussionmentioning

confidence: 99%

WNT3 promotes chemoresistance to 5-Fluorouracil in oral squamous cell carcinoma via activating the canonical β-catenin pathway

Zhang,

Sun,

Gan

et al. 2024

BMC Cancer

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Background 5-Fluorouracil (5FU) is a primary chemotherapeutic agent used to treat oral squamous cell carcinoma (OSCC). However, the development of drug resistance has significantly limited its clinical application. Therefore, there is an urgent need to determine the mechanisms underlying drug resistance and identify effective targets. In recent years, the Wingless and Int-1 (WNT) signaling pathway has been increasingly studied in cancer drug resistance; however, the role of WNT3, a ligand of the canonical WNT signaling pathway, in OSCC 5FU-resistance is not clear. This study delved into this potential connection. Methods 5FU-resistant cell lines were established by gradually elevating the drug concentration in the culture medium. Differential gene expressions between parental and resistant cells underwent RNA sequencing analysis, which was then substantiated via Real-time quantitative PCR (RT-qPCR) and western blot tests. The influence of the WNT signaling on OSCC chemoresistance was ascertained through WNT3 knockdown or overexpression. The WNT inhibitor methyl 3-benzoate (MSAB) was probed for its capacity to boost 5FU efficacy. Results In this study, the WNT/β-catenin signaling pathway was notably activated in 5FU-resistant OSCC cell lines, which was confirmed through transcriptome sequencing analysis, RT-qPCR, and western blot verification. Additionally, the key ligand responsible for pathway activation, WNT3, was identified. By knocking down WNT3 in resistant cells or overexpressing WNT3 in parental cells, we found that WNT3 promoted 5FU-resistance in OSCC. In addition, the WNT inhibitor MSAB reversed 5FU-resistance in OSCC cells. Conclusions These data underscored the activation of the WNT/β-catenin signaling pathway in resistant cells and identified the promoting effect of WNT3 upregulation on 5FU-resistance in oral squamous carcinoma. This may provide a new therapeutic strategy for reversing 5FU-resistance in OSCC cells.

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“… 313 Early diagnosis holds the potential to positively impact the survival rates of OSCC. Research indicates that Notch receptors, specifically Notch1, 314 , 315 Notch3, 316 and Notch4, 317 , 318 exhibit high levels in human OSCC tissues and are associated with a poor prognosis. This suggests that Notch receptors could serve as biomarkers for the early diagnosis of OSCC.…”

Section: The Notch Signaling Pathway and Cancermentioning

confidence: 99%

Notch signaling pathway in cancer: from mechanistic insights to targeted therapies

Shi,

Xue,

Zeng

et al. 2024

Sig Transduct Target Ther

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Notch signaling, renowned for its role in regulating cell fate, organ development, and tissue homeostasis across metazoans, is highly conserved throughout evolution. The Notch receptor and its ligands are transmembrane proteins containing epidermal growth factor-like repeat sequences, typically necessitating receptor-ligand interaction to initiate classical Notch signaling transduction. Accumulating evidence indicates that the Notch signaling pathway serves as both an oncogenic factor and a tumor suppressor in various cancer types. Dysregulation of this pathway promotes epithelial-mesenchymal transition and angiogenesis in malignancies, closely linked to cancer proliferation, invasion, and metastasis. Furthermore, the Notch signaling pathway contributes to maintaining stem-like properties in cancer cells, thereby enhancing cancer invasiveness. The regulatory role of the Notch signaling pathway in cancer metabolic reprogramming and the tumor microenvironment suggests its pivotal involvement in balancing oncogenic and tumor suppressive effects. Moreover, the Notch signaling pathway is implicated in conferring chemoresistance to tumor cells. Therefore, a comprehensive understanding of these biological processes is crucial for developing innovative therapeutic strategies targeting Notch signaling. This review focuses on the research progress of the Notch signaling pathway in cancers, providing in-depth insights into the potential mechanisms of Notch signaling regulation in the occurrence and progression of cancer. Additionally, the review summarizes pharmaceutical clinical trials targeting Notch signaling for cancer therapy, aiming to offer new insights into therapeutic strategies for human malignancies.

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Prognostic Value of WNT1, NOTCH1, PDGFRβ, and CXCR4 in Oral Squamous Cell Carcinoma

Cited by 6 publications

References 0 publications

WNT3 promotes chemoresistance to 5-Fluorouracil in oral squamous cell carcinoma via activating the canonical β-catenin pathway

WNT3 promotes chemoresistance to 5-Fluorouracil in oral squamous cell carcinoma via activating the canonical β-catenin pathway

WNT3 promotes chemoresistance to 5-Fluorouracil in oral squamous cell carcinoma via activating the canonical β-catenin pathway

Notch signaling pathway in cancer: from mechanistic insights to targeted therapies

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