Role of Met Axis in Head and Neck Cancer

Abstract

Head and neck cancer is the sixth most common type of cancer worldwide. Despite advances in aggressive multidisciplinary treatments, the 5-year survival rate for this dreadful disease is only 50%, mostly due to high rate of recurrence and early involvement of regional lymph nodes and subsequent metastasis. Understanding the molecular mechanisms responsible for invasion and metastasis is one of the most pressing goals in the field of head and neck cancer. Met, also known as hepatocyte growth factor receptor (HGFR), is a member of the receptor protein tyrosine kinase (RPTK) family. There is compelling evidence that Met axis is dysregulated and plays important roles in tumorigenesis, progression, metastasis, angiogenesis, and drug resistance in head and neck cancer. We describe in this review current understanding of Met axis in head and neck cancer biology and development of therapeutic inhibitors targeting Met axis.

MicroRNAs and head and neck cancer: Reviewing the first decade of research

“…This is perhaps counter-intuitive as miR-34b has been shown to act as a tumour-suppressor in a feedback loop with the proto-oncogene Met [147]. Over-expression of the Met-axis has been correlated with progression and metastases in HNSCC [148].…”

Tyrosine Kinase c-MET as Therapeutic Target for Radiosensitization of Head and Neck Squamous Cell Carcinomas

“…A major signaling pathway contributing to tumor cell resistance is the PI3K/AKT signal pathway activated through EGFR [ 9 , 10 ]. EGFR and c-MET proteins are closely linked at the cell membrane and activate common downstream signaling pathways such as RAS/RAF/ERK, PI3K/AKT, and JAK/STAT [ 11 , 12 ]. Several clinical studies, including data from our institute, demonstrated that increased MET gene expression significantly correlates with reduced locoregional control, decreased overall survival and enhanced distant metastasis after post-operative radio(chemo)therapy, especially in patients with human papillomavirus (HPV)-negative HNSCC, while it does not have prognostic potential in patients treated with primary radio(chemo)therapy [ 11 , 13 , 14 , 15 , 16 ].…”

Role of E-cadherin and cyclin D1 as predictive markers of aggression and clonal expansion in head and neck squamous cell carcinoma

“…Despite an aggressive multidisciplinary approach and advances in treatment, the 5-year survival rate for HNSCC has not improved much 4 . Although a number of factors such as TNM stage 5 6 , histologic grade of tumour 7 8 , perineural invasion 8 9 , depth of tumour 8 , and extracapsular spread 10 11 have been used as prognostic markers in HNSCC, regional lymph node (LN) metastasis has been considered one of the most important factors determining treatment approach and thus long-term survival 8 10 11 12 .…”

“…It is a cell adhesion molecule that connects epithelial cells via homotypic interaction. Disruption of this interaction promotes detachment of cancer cells from their primary sites, the first step in the tumour invasion process 4 . Reduced or aberrant E-cadherin expression appears to be associated with various parameters such as aggressiveness of tumour, enhanced invasion, and metastatic potential in a number of malignancies including HNSCC 20 21 22 23 .…”