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J Cell Commun Signal. 2018 Dec;12(4):709-721. doi: 10.1007/s12079-017-0442-2. Epub 2018 Feb 26.

Role of protein kinase N2 (PKN2) in cigarette smoke-mediated oncogenic transformation of oral cells.

Author information

1
Institute of Bioinformatics, 7th floor, Discoverer Building, International Tech Park, Bangalore, 560 066, India.
2
School of Biotechnology, Kalinga Institute of Industrial Technology, Bhubaneswar, 751024, India.
3
School of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam, 690 525, India.
4
Department of Biochemistry & Molecular Biology, Pondicherry University, Pondicherry, 605014, India.
5
NIMHANS-IOB Bioinformatics and Proteomics Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences, Bangalore, 560 029, India.
6
Center for Systems Biology and Molecular Medicine, Yenepoya, Mangalore, 575020, India.
7
Department of Surgery, UC San Diego, Moores Cancer Center, La Jolla, CA, 92093, USA.
8
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.
9
Institute of Bioinformatics, 7th floor, Discoverer Building, International Tech Park, Bangalore, 560 066, India. harsha@ibioinformatics.org.
10
Institute of Bioinformatics, 7th floor, Discoverer Building, International Tech Park, Bangalore, 560 066, India. aditi@ibioinformatics.org.

Abstract

Smoking is the leading cause of preventable death worldwide. Though cigarette smoke is an established cause of head and neck cancer (including oral cancer), molecular alterations associated with chronic cigarette smoke exposure are poorly studied. To understand the signaling alterations induced by chronic exposure to cigarette smoke, we developed a cell line model by exposing normal oral keratinocytes to cigarette smoke for a period of 12 months. Chronic exposure to cigarette smoke resulted in increased cellular proliferation and invasive ability of oral keratinocytes. Proteomic and phosphoproteomic analyses showed dysregulation of several proteins involved in cellular movement and cytoskeletal reorganization in smoke exposed cells. We observed overexpression and hyperphosphorylation of protein kinase N2 (PKN2) in smoke exposed cells as well as in a panel of head and neck cancer cell lines established from smokers. Silencing of PKN2 resulted in decreased colony formation, invasion and migration in both smoke exposed cells and head and neck cancer cell lines. Our results indicate that PKN2 plays an important role in oncogenic transformation of oral keratinocytes in response to cigarette smoke. The current study provides evidence that PKN2 can act as a potential therapeutic target in head and neck squamous cell carcinoma, especially in patients with a history of smoking.

KEYWORDS:

Carcinogenesis; Cell adhesion; High-throughput; Orbitrap fusion; Smoking

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