Interaction between N-cadherin and decoy receptor-2 regulates apoptosis in head and neck cancer
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Phuong Thao Nguyen1,2,3, Dung Nguyen1, Chanbora Chea1, Mutsumi Miyauchi1, Makiko Fujii3 and Takashi Takata1
1Department of Oral and Maxillofacial Pathobiology, Basic Life Science, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
2Department of General Internal Medicine, Hiroshima University Hospital, Hiroshima, Japan
3Department of Global Dental Medicine and Molecular Oncology, Integrated Health Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
Phuong Thao Nguyen, email: firstname.lastname@example.org
Takashi Takata, email: email@example.com
Keywords: N-cadherin; DR-5, DcR-2; anti-apoptosis; death receptors
Received: January 11, 2017 Accepted: July 15, 2018 Published: July 31, 2018
N-cadherin is a neural cell adhesion molecule that aberrantly occurs in head and neck cancers to promote cancer cell growth. However, the underlying mechanisms remain unclear. Here we report that N-cadherin increases cancer cell growth by inhibiting apoptosis. Apoptosis eliminates old, unnecessary, and unhealthy cells. However, tumor cells have the ability of avoiding apoptosis that increases cancer cell growth. Recent studies have found that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in tumor cells by reacting with four distinct cell surface receptors: TRAIL-R1 (DR-4), TRAIL-R2 (DR-5), TRAIL-R3 (DcR-1), and TRAIL-R4 (DcR-2). Among these TRAIL receptors, the death receptors DR-4 and DR-5 transmit apoptotic signals owing to the death domain in the intracellular portion. Conversely, the decoy receptors DcR-1 and DcR-2 lack a complete intracellular portion, so neither can transmit apoptotic signals. DcR-1 or DcR-2 overexpression suppresses TRAIL-induced apoptosis.
In this study, N-cadherin overexpression increased DcR-2 expression and decreased DR-5 expression. In contrast, knockdown of N-cadherin expression upregulated DR-5 expression and downregulated DcR-2 expression. A significantly positive relationship between N-cadherin and DcR-2 expression was also found in HNSCC specimens. Those specimens with a lower apoptotic index showed a higher expression of N-cadherin and/or DcR-2. In addition, we demonstrated that N-cadherin interacts directly with DcR-2. Notably, DcR-2 induces cancer cell survival through the cleavage of caspases and PARP by activating MAPK/ERK pathway and suppressing NF-kB/ p65 phosphorylation, which has a very important role in resistance to chemotherapy.
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