Collagen induces a more proliferative, migratory and chemoresistant phenotype in head and neck cancer via DDR1

Research output: Contribution to journalArticlepeer-review

Authors

  • Sook Ling Lai
  • May Leng Tan
  • Robert J Hollows
  • Max Robinson
  • Maha Ibrahim
  • Sandra Margielewska
  • E Kenneth Parkinson
  • Anand Ramanathan
  • Rosnah Binti Zain
  • Ivy Chung
  • Paul G Murray
  • Lee Fah Yap
  • Ian C Paterson

External organisations

  • Newcastle University
  • University of Malaya
  • Assiut University
  • Queen Mary University of London
  • MAHSA University
  • Durham University
  • University of Limerick

Abstract

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.

Details

Original languageEnglish
Article number1766
Pages (from-to)1-16
Number of pages16
JournalCancers
Volume11
Issue number11
Publication statusPublished - 9 Nov 2019

Keywords

  • head and neck cancer, collagen, DDR1