Cancers, Vol. 11, Pages 1766: Collagen Induces a More Proliferative, Migratory and Chemoresistant Phenotype in Head and Neck Cancer via DDR1

Cancers, Vol. 11, Pages 1766: Collagen Induces a More Proliferative, Migratory and Chemoresistant Phenotype in Head and Neck Cancer via DDR1 Cancers doi: 10.3390/cancers11111766 Authors: Sook Ling Lai May Leng Tan Robert J. Hollows Max Robinson Maha Ibrahim Sandra Margielewska E. Kenneth Parkinson Anand Ramanathan Rosnah Binti Zain Hisham Mehanna Rachel J. Spruce Wenbin Wei Ivy Chung Paul G. Murray Lee Fah Yap Ian C. Paterson Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and includes squamous cell carcinomas of the oropharynx and oral cavity. Patient prognosis has remained poor for decades and molecular targeted therapies are not in routine use. Here we showed that the overall expression of collagen subunit genes was higher in cancer-associated fibroblasts (CAFs) than normal fibroblasts. Focusing on collagen8A1 and collagen11A1, we showed that collagen is produced by both CAFs and tumour cells, indicating that HNSCCs are collagen-rich environments. We then focused on discoidin domain receptor 1 (DDR1), a collagen-activated receptor tyrosine kinase, and showed that it is over-expressed in HNSCC tissues. Further, we demonstrated that collagen promoted the proliferation and migration of HNSCC cells and attenuated the apoptotic response to cisplatin. Knockdown of DDR1 in HNSCC cells demonstrated that these tumour-promoting effects of collagen are mediated by DDR1. Our data suggest that specific inhibi...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research

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