Publication:
Toll-like recepwtor 2 induces adenosine receptor A2a and promotes human squamous carcinoma cell growth via extracellular signal regulated kinases 1/2

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Issued Date

2018

Resource Type

Article

File Type

application/pdf

ISSN

19492553

DOI

10.18632/oncotarget.23784

Other identifier(s)

2-s2.0-85040926472

Rights Holder(s)

Scopus

Bibliographic Citation

Oncotarget. Vol 9, No.6 (2018), p.6814-6829

Suggested Citation

Palani C.D., Ramanathapuram L., Lam-Ubol A., Kurago Z.B. Toll-like recepwtor 2 induces adenosine receptor A2a and promotes human squamous carcinoma cell growth via extracellular signal regulated kinases 1/2. Oncotarget. Vol 9, No.6 (2018), p.6814-6829. doi:10.18632/oncotarget.23784 Retrieved from: https://hdl.handle.net/20.500.14740/3962

Title

Toll-like recepwtor 2 induces adenosine receptor A2a and promotes human squamous carcinoma cell growth via extracellular signal regulated kinases 1/2

Author(s)

Palani C.D.
 Ramanathapuram L.
 Lam-Ubol A.
 Kurago Z.B.

Abstract

Patient treatment for oral squamous cell carcinoma (OSCC) not associated with Human papillomavirus remains problematic. OSCC microenvironment is typically inflamed and colonized by microorganisms, providing ligands for toll-like receptors (TLR). In immune cells TLR2 and TLR4 activate NF-kB and extracellular signal regulated kinase (ERK)1/2 pathways, leading to upregulation of inhibitory adenosine receptors A2a and A2b, and reduction in stimulatory A1 and A3. How TLR and adenosine receptors function in SCC cells is not understood. To address this gap, we evaluated TLR and adenosine receptor expression and function in human OSCC cells and keratinocytes. TLR2 and A2a were co-expressed in pre-cancer and SCC cells of 17 oral specimens. In vitro, 5/6 OSCC lines expressed more TLR2 than TLR1, 4 or 6 mRNA. TLR2 ligands stimulated A2a expression in TLR2-high cell lines, but no A1 or A3 was detected with or without stimuli. In TLR2-high OSCC, TLR2/1, 2/6 and adenosine receptor agonists activated ERK1/2. TLR2-mediated ERK1/2 phosphorylation resulted in accumulation of c-FOS, ERK-dependent cell proliferation and reduced caspase-3 activity. Similar ERK1/2-dependent proliferation and decreased caspase-3 activity were caused by combined TLR2 and adenosine receptor stimuli. We conclude that TLR2 and adenosine receptor agonists, known to be present in the tumor microenvironment, may contribute to OSCC progression in part via direct effects on the ERK1/2 pathway in squamous carcinoma cells. © Palani et al.

Subject(s)

Adenosine A2a receptor
 Caspase 3
 Messenger RNA
 Mitogen activated protein kinase 1
 Mitogen activated protein kinase 3
 Protein c fos
 Toll like receptor 1
 Toll like receptor 2
 Toll like receptor 4
 Toll like receptor 6
 Article
 Bioaccumulation
 Cancer growth
 Cell proliferation
 Clinical article
 Controlled study
 Enzyme activation
 Enzyme activity
 Enzyme phosphorylation
 Human
 Human cell
 Human tissue
 In vitro study
 Keratinocyte
 Mouth squamous cell carcinoma
 Oral squamous cell carcinoma cell line
 Protein expression
 Protein function
 Protein induction
 TLR signaling
 Tumor promotion

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URI

https://hdl.handle.net/20.500.14740/3962

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Scopus: Year 1983-2021

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