Collagen Induces a More Proliferative, Migratory and Chemoresistant Phenotype in Head and Neck Cancer via DDR1
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 ex...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI
2019
|
| Subjects: | |
| Online Access: | http://eprints.um.edu.my/23886/1/cancers-11-01766%20%284%29.pdf http://eprints.um.edu.my/23886/ https://www.mdpi.com/2072-6694/11/11/1766/htm |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| id |
my.um.eprints.23886 |
|---|---|
| record_format |
eprints |
| spelling |
my.um.eprints.238862020-02-21T03:18:23Z http://eprints.um.edu.my/23886/ Collagen Induces a More Proliferative, Migratory and Chemoresistant Phenotype in Head and Neck Cancer via DDR1 Lai, Sook Ling Tan, May Leng Hollows, Robert J. Robinson, Max Ibrahim, Maha Margielewska, Sandra Parkinson, E. Kenneth Ramanathan, Anand Zain, R.B. Mehanna, Hisham Spruce, Rachel J. Wei, Wenbin Chung, Ivy Murray, Paul G. Yap, Lee Fah Paterson, Ian Charles R Medicine RC0254 Neoplasms. Tumors. Oncology (including Cancer) RK Dentistry Practice of dentistry. Dental economics 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. MDPI 2019 Article PeerReviewed text en http://eprints.um.edu.my/23886/1/cancers-11-01766%20%284%29.pdf 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, R.B. and Mehanna, Hisham and Spruce, Rachel J. and Wei, Wenbin and Chung, Ivy and Murray, Paul G. and Yap, Lee Fah and Paterson, Ian Charles (2019) Collagen Induces a More Proliferative, Migratory and Chemoresistant Phenotype in Head and Neck Cancer via DDR1. Cancers, 11 (11). p. 1766. ISSN 2072-6694 https://www.mdpi.com/2072-6694/11/11/1766/htm doi:10.3390/cancers11111766 |
| institution |
Universiti Malaya |
| building |
UM Library |
| collection |
Institutional Repository |
| continent |
Asia |
| country |
Malaysia |
| content_provider |
Universiti Malaya |
| content_source |
UM Research Repository |
| url_provider |
http://eprints.um.edu.my/ |
| language |
English |
| topic |
R Medicine RC0254 Neoplasms. Tumors. Oncology (including Cancer) RK Dentistry Practice of dentistry. Dental economics |
| spellingShingle |
R Medicine RC0254 Neoplasms. Tumors. Oncology (including Cancer) RK Dentistry Practice of dentistry. Dental economics Lai, Sook Ling Tan, May Leng Hollows, Robert J. Robinson, Max Ibrahim, Maha Margielewska, Sandra Parkinson, E. Kenneth Ramanathan, Anand Zain, R.B. Mehanna, Hisham Spruce, Rachel J. Wei, Wenbin Chung, Ivy Murray, Paul G. Yap, Lee Fah Paterson, Ian Charles Collagen Induces a More Proliferative, Migratory and Chemoresistant Phenotype in Head and Neck Cancer via DDR1 |
| description |
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. |
| format |
Article |
| author |
Lai, Sook Ling Tan, May Leng Hollows, Robert J. Robinson, Max Ibrahim, Maha Margielewska, Sandra Parkinson, E. Kenneth Ramanathan, Anand Zain, R.B. Mehanna, Hisham Spruce, Rachel J. Wei, Wenbin Chung, Ivy Murray, Paul G. Yap, Lee Fah Paterson, Ian Charles |
| author_facet |
Lai, Sook Ling Tan, May Leng Hollows, Robert J. Robinson, Max Ibrahim, Maha Margielewska, Sandra Parkinson, E. Kenneth Ramanathan, Anand Zain, R.B. Mehanna, Hisham Spruce, Rachel J. Wei, Wenbin Chung, Ivy Murray, Paul G. Yap, Lee Fah Paterson, Ian Charles |
| author_sort |
Lai, Sook Ling |
| title |
Collagen Induces a More Proliferative, Migratory and Chemoresistant Phenotype in Head and Neck Cancer via DDR1 |
| title_short |
Collagen Induces a More Proliferative, Migratory and Chemoresistant Phenotype in Head and Neck Cancer via DDR1 |
| title_full |
Collagen Induces a More Proliferative, Migratory and Chemoresistant Phenotype in Head and Neck Cancer via DDR1 |
| title_fullStr |
Collagen Induces a More Proliferative, Migratory and Chemoresistant Phenotype in Head and Neck Cancer via DDR1 |
| title_full_unstemmed |
Collagen Induces a More Proliferative, Migratory and Chemoresistant Phenotype in Head and Neck Cancer via DDR1 |
| title_sort |
collagen induces a more proliferative, migratory and chemoresistant phenotype in head and neck cancer via ddr1 |
| publisher |
MDPI |
| publishDate |
2019 |
| url |
http://eprints.um.edu.my/23886/1/cancers-11-01766%20%284%29.pdf http://eprints.um.edu.my/23886/ https://www.mdpi.com/2072-6694/11/11/1766/htm |
| _version_ |
1662755192985092096 |
| score |
13.211869 |