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

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

doi:10.3390/cancers11111766

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

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

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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.

Original language	English
Article number	1766
Pages (from-to)	1-16
Number of pages	16
Journal	Cancers
Volume	11
Issue number	11
DOIs	https://doi.org/10.3390/cancers11111766
Publication status	Published - 9 Nov 2019

Keywords

head and neck cancer
collagen
DDR1

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Lai_et_al_Collagen_induces_Cancers_2019Final published version, 2.74 MBLicence: Creative Commons: Attribution (CC BY)

https://www.mdpi.com/2072-6694/11/11/1766Licence: Creative Commons: Attribution (CC BY)

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Lai, S. L., Tan, M. L., Hollows, R. J., Robinson, M., Ibrahim, M., Margielewska, S., Parkinson, E. K., Ramanathan, A., Zain, R. B., Mehanna, H., Spruce, R. J., Wei, W., Chung, I., Murray, P. G., Yap, L. F., & Paterson, I. C. (2019). Collagen induces a more proliferative, migratory and chemoresistant phenotype in head and neck cancer via DDR1. Cancers, 11(11), 1-16. Article 1766 . https://doi.org/10.3390/cancers11111766

@article{59abdd924fb14ff1941bb79f634629d9,

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

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.",

keywords = "head and neck cancer, collagen, DDR1",

author = "Lai, {Sook Ling} and Tan, {May Leng} and Hollows, {Robert J} and Max Robinson and Maha Ibrahim and Sandra Margielewska and Parkinson, {E Kenneth} and Anand Ramanathan and Zain, {Rosnah Binti} and Hisham Mehanna and Spruce, {Rachel J} and Wenbin Wei and Ivy Chung and Murray, {Paul G} and Yap, {Lee Fah} and Paterson, {Ian C}",

year = "2019",

month = nov,

day = "9",

doi = "10.3390/cancers11111766",

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volume = "11",

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Lai, SL, Tan, ML, Hollows, RJ, Robinson, M, Ibrahim, M, Margielewska, S, Parkinson, EK, Ramanathan, A, Zain, RB, Mehanna, H, Spruce, RJ, Wei, W, Chung, I, Murray, PG, Yap, LF & Paterson, IC 2019, 'Collagen induces a more proliferative, migratory and chemoresistant phenotype in head and neck cancer via DDR1', Cancers, vol. 11, no. 11, 1766 , pp. 1-16. https://doi.org/10.3390/cancers11111766

TY - JOUR

T1 - Collagen induces a more proliferative, migratory and chemoresistant phenotype in head and neck cancer via DDR1

AU - Lai, Sook Ling

AU - Tan, May Leng

AU - Hollows, Robert J

AU - Robinson, Max

AU - Ibrahim, Maha

AU - Margielewska, Sandra

AU - Parkinson, E Kenneth

AU - Ramanathan, Anand

AU - Zain, Rosnah Binti

AU - Mehanna, Hisham

AU - Spruce, Rachel J

AU - Wei, Wenbin

AU - Chung, Ivy

AU - Murray, Paul G

AU - Yap, Lee Fah

AU - Paterson, Ian C

PY - 2019/11/9

Y1 - 2019/11/9

N2 - 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.

AB - 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.

KW - head and neck cancer

KW - collagen

KW - DDR1

U2 - 10.3390/cancers11111766

DO - 10.3390/cancers11111766

M3 - Article

C2 - 31717573

SN - 2072-6694

VL - 11

SP - 1

EP - 16

JO - Cancers

JF - Cancers

IS - 11

M1 - 1766

ER -

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

Abstract

Keywords

UN SDGs

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