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Cancers 2019, 11(1), 107; https://doi.org/10.3390/cancers11010107

FOSB–PCDHB13 Axis Disrupts the Microtubule Network in Non-Small Cell Lung Cancer

1
Marine Research Station, Institute of Cellular and Organismic Biology, Academia Sinica, Ilan 262, Taiwan
2
Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
3
Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City 235, Taiwan
4
Division of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
5
The iEGG and Animal Biotechnology Center, National Chung Hsing University, Taichung 402, Taiwan
6
Center of Excellence for the Oceans, National Taiwan Ocean University, Keelung 202, Taiwan
*
Author to whom correspondence should be addressed.
Received: 18 December 2018 / Revised: 14 January 2019 / Accepted: 14 January 2019 / Published: 17 January 2019
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Abstract

Non-small cell lung cancer (NSCLC) is among the leading causes of human mortality. One reason for high rates of NSCLC mortality is that drug resistance is a major problem for both conventional chemotherapies and less-toxic targeted therapies. Thus, novel mechanistic insights into disease pathogenesis may benefit the development of urgently needed therapies. Here we show that FBJ murine osteosarcoma viral oncogene homolog B (FOSB) was induced by an antimicrobial peptide, tilapia piscidin-4 (TP4), through the dysregulation of mitochondrial Ca2+ homeostasis in NSCLC cells. Transcriptomic, chromatin immunoprecipitation quantitative PCR, and immunocytochemical studies reveal that protocadherin-β13 (PCDHB13) as a target of FOSB that was functionally associated with microtubule. Overexpression of either PCDHB13 or FOSB attenuated NSCLC growth and survival in vitro and in vivo. Importantly, downregulation of both FOSB and PCDHB13 was observed in NSCLC patients and was negatively correlated with pathological grade. These findings introduce the FOSB–PCDHB13 axis as a novel tumor suppressive pathway in NSCLC. View Full-Text
Keywords: antimicrobial peptide; mitochondrial stress; FOSB; protocadherin; cytoskeleton; non-small cell lung cancer (NSCLC) antimicrobial peptide; mitochondrial stress; FOSB; protocadherin; cytoskeleton; non-small cell lung cancer (NSCLC)
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Ting, C.-H.; Lee, K.-Y.; Wu, S.-M.; Feng, P.-H.; Chan, Y.-F.; Chen, Y.-C.; Chen, J.-Y. FOSB–PCDHB13 Axis Disrupts the Microtubule Network in Non-Small Cell Lung Cancer. Cancers 2019, 11, 107.

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