Harishankar Mk1, Sharon Prince2, A Mathan Mohan3, K Vinod Krishnan3, Arikketh Devi4. 1. Department of Genetic Engineering, School of Bioengineering, SRM University, Kattankulathur 603203, India. 2. Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Cape Town, , South Africa. 3. Department of Oral and Maxillofacial Surgery, Karpaga Vinayaga Institute of Dental Sciences, Kancheepuram 603308, India. 4. Department of Genetic Engineering, School of Bioengineering, SRM University, Kattankulathur 603203, India. Electronic address: adevipradeep@gmail.com.
Abstract
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.
AIMS: Despite the development of several therapeutic strategies in the past decades, clinicians have failed to improve the survival rate of oral squamous cell carcinomapatients 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.
Authors: Deri Morgan; Kiersten L Berggren; Colby D Spiess; Hannah M Smith; Ajay Tejwani; Scott J Weir; Christopher E Lominska; Sufi M Thomas; Gregory N Gan Journal: Mol Carcinog Date: 2021-09-24 Impact factor: 4.784
Authors: Anjali P Patni; M K Harishankar; Joel P Joseph; Bhuvanadas Sreeshma; Rama Jayaraj; Arikketh Devi Journal: Cell Oncol (Dordr) Date: 2021-03-11 Impact factor: 6.730
Authors: Yasmin Ghantous; Mohamed Omar; Esther Channah Broner; Nishant Agrawal; Alexander T Pearson; Ari J Rosenberg; Vasudha Mishra; Alka Singh; Imad Abu El-Naaj; Peter A Savage; David Sidransky; Luigi Marchionni; Evgeny Izumchenko Journal: Int J Cancer Date: 2021-10-14 Impact factor: 7.396