Lai, Sook Ling and Tan, May Leng and Hollows, Robert J. and Robinson, Max and Ibrahim, Maha and Margielewska, Sandra and Parkinson, E. Kenneth and Ramanathan, Anand and Zain, Rosnah Binti and Mehanna, Hisham and Spruce, Rachel J. and Wei, Wenbin and Chung, Ivy and Murray, Paul G. and Yap, Lee Fah and Paterson, Ian C. (2019) 'Collagen induces a more proliferative, migratory and chemoresistant phenotype in head and neck cancer via DDR1.', Cancers., 11 (11). p. 1766.
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 inhibitors of DDR1 might provide novel therapeutic opportunities to treat HNSCC.
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|Publisher Web site:||https://doi.org/10.3390/cancers11111766|
|Publisher statement:||This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.|
|Date accepted:||05 November 2019|
|Date deposited:||22 November 2019|
|Date of first online publication:||09 November 2019|
|Date first made open access:||22 November 2019|
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