Related Experiment Video
Updated: Mar 21, 2026
Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
Published on: January 12, 2020
Association of Notch4 with metastasis in human oral squamous cell carcinoma
Harishankar Mk1, Sharon Prince2, A Mathan Mohan3
1Department of Genetic Engineering, School of Bioengineering, SRM University, Kattankulathur 603203, India.
Aims:
Despite the development of several therapeutic strategies in the past decades, clinicians have failed to improve the survival rate of oral squamous cell carcinoma patients due to the highly metastatic nature of the disease and its high recurrence rate. However, there is accumulating evidence that aberrant Notch4 expression has a critical role in tumorigenesis but its prognostic value and function in OSCC remains uncertain. This study therefore investigates (1) the expression of Notch4 and its downstream target, myelin associated glycoprotein (MAG) in tissue samples representative of different stages of OSCC with varied clinicopathological features and (2) the possible involvement of Notch4 in the proliferation and migration of OSCC cells.
Main Methods:
Sixty patients reported positive for OSCC were obtained along with the clinicopathological parameters and we performed immunohistochemistry, western blotting and RT-PCR for Notch4 and MAG expression. Further, the metastatic role of Notch4 was analyzed in the HSC-3 cell line by cell proliferation and migration assays.
Key Findings:
Our findings reveal that Notch4 and MAG expression are significantly upregulated in specifically late stages of OSCC tumor sections and perineural invasion (PNI) positive cases. In addition, depletion of Notch4 by siRNA inhibited the proliferative and migratory ability of the highly metastatic HSC-3 OSCC cells.
Significance:
Our study indicates that the aberrant activation of Notch4 promotes OSCC metastasis through perineural spread and ascertains its value as a significant prognostic marker and potential therapeutic target to treat this highly aggressive malignancy.
Insights
Aberrant Notch4 activation promotes oral squamous cell carcinoma (OSCC) metastasis via perineural invasion. Targeting Notch4 offers a potential therapeutic strategy for this aggressive cancer.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Oral squamous cell carcinoma (OSCC) survival rates remain poor due to high metastasis and recurrence.
- The role and prognostic value of Notch4 in OSCC are not well-defined.
- Notch4 is implicated in tumorigenesis, but its specific function in OSCC progression is uncertain.
Purpose of the Study:
- To investigate Notch4 and myelin associated glycoprotein (MAG) expression in various OSCC stages and clinicopathological features.
- To determine the prognostic significance of Notch4 in OSCC.
- To elucidate the functional role of Notch4 in OSCC cell proliferation and migration.
Main Methods:
- Immunohistochemistry, western blotting, and RT-PCR were used to assess Notch4 and MAG expression in 60 OSCC patient samples.
- Clinicopathological parameters were analyzed alongside molecular expression data.
- Notch4's metastatic role was evaluated in HSC-3 OSCC cells using proliferation and migration assays after siRNA-mediated depletion.
Main Results:
- Notch4 and MAG expression were significantly upregulated in late-stage OSCC and in cases with perineural invasion (PNI).
- Depletion of Notch4 using siRNA reduced the proliferation and migration of highly metastatic HSC-3 cells.
- These findings link Notch4 upregulation to advanced OSCC and metastatic potential.
Conclusions:
- Aberrant Notch4 activation drives OSCC metastasis, particularly through perineural spread.
- Notch4 serves as a valuable prognostic marker for OSCC.
- Targeting Notch4 presents a potential therapeutic strategy for managing aggressive OSCC.
Related Concept Videos
03:14Notch Signaling Pathway
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
03:14Notch Signaling Pathway
01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
02:30Metastasis
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
02:30Metastasis
01:41Non-Canonical Wnt Signaling Pathways