Oncotarget

Research Papers:

TrkB promotes laryngeal cancer metastasis via activation PI3K/AKT pathway

Liang Jiang, Zhihai Wang, Chuan Liu, Zhitao Gong, Yucheng Yang, Houyong Kang, Yanshi Li and Guohua Hu _

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Oncotarget. 2017; 8:108726-108737. https://doi.org/10.18632/oncotarget.21711

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Abstract

Liang Jiang1,2, Zhihai Wang1, Chuan Liu1, Zhitao Gong1, Yucheng Yang1, Houyong Kang1, Yanshi Li1 and Guohua Hu1

1Department of Otolaryngology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016 China

2Department of Otolaryngology Head and Neck Surgery, Affiliated Hospital of Southwest Medical University, Luzhou, 646000 China

Correspondence to:

Guohua Hu, email: [email protected]

Keywords: TrkB; laryngeal cancer; PI3K/AKT pathway; tumorigenicity

Received: May 17, 2017    Accepted: August 17, 2017    Published: October 09, 2017

ABSTRACT

Objectives: The aim of our study was to investigate the role of TrkB pathway in tumor occurrence and development for in order to provide theoretical basis to laryngeal cancer therapy.

Materials and methods: Biological characteristics of the cells were studied by migration tests and colony forming assay. Gene and protein expression analysis was performed by RT-PCR or western blot. in vivo experiments were conducted in syngeneic BALB/c mice.

Results: Significant changes in protein and gene expression, including higher expression level of TrkB, were found in cells and laryngeal cancer specimens. we demonstrated that TrkB activates AKT via c-Src, leading to increased proliferation. Also, TrkB induced EMT via increased expression of EMT related transcription factors such as Twist-1 and Twist-2.

Conclusion: Our data indicate TrkB are overexpressed in laryngeal cancer, and TrkB signaling is involved in tumorigenicity of laryngeal cancer. These observations suggest that TrkB is a promising target for future intervention strategies to prevent tumor metastasis, EMT program in laryngeal cancer.

What is already known about this subject?

• Cancer of the larynx is one of the most common types of head and neck cancer.

• The survival rate of advanced laryngeal cancer is only 30 to 40%.

• The tropomyosin-related kinase B receptor (TrkB), together with TrkA and TrkC, are neurotrophin receptors regulating the proliferation and differentiation of neuronal cells.

What are the new findings?

• TrkB are overexpressed in laryngeal cancer.

• TrkB signaling is involved in tumorigenicity of laryngeal cancer.

• TrkB acts as a key regulator of the PI3K/AKT signal pathway-mediated tumor metastasis.

How might these results change the focus of research or clinical practice?

• These observations suggest that TrkB is a promising target for future intervention strategies to prevent tumor metastasis, EMT program in laryngeal cancer. Our study provides molecular insight into the tumor metastasis and has important implications in elucidating oncogenic processes.


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