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Journal of Experimental & Clinical Cancer Research

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Open Access 01-12-2019 | NSCLC | Research

Nck-associated protein 1 associates with HSP90 to drive metastasis in human non-small-cell lung cancer

Authors: Yuanping Xiong, Leilei He, Chloe Shay, Liwei Lang, Jenni Loveless, Jieqing Yu, Ron Chemmalakuzhy, Hongqun Jiang, Manran Liu, Yong Teng

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2019

Abstract

Background

Metastatic lung cancer is a life-threatening condition that develops when cancer in another area of the body metastasizes, or spreads, to the lung. Despite advances in our understanding of primary lung oncogenesis, the biological basis driving the progression from primary to metastatic lung cancer remains poorly characterized.

Methods

Genetic knockdown of the particular genes in cancer cells were achieved by lentiviral-mediated interference. Invasion potential was determined by Matrigel and three-dimensional invasion. The secretion of matrix metalloproteinase 2 (MMP2) and MMP9 were measured by ELISA. Protein levels were assessed by Western blotting and immunohistochemistry. Protein-protein interactions were determined by immunoprecipitation. An experimental mouse model was generated to investigate the gene regulation in tumor growth and metastasis.

Results

Nck-associated protein 1 (NAP1/NCKAP1) is highly expressed in primary non-small-cell lung cancer (NSCLC) when compared with adjacent normal lung tissues, and its expression levels are strongly associated with the histologic tumor grade, metastasis and poor survival rate of NSCLC patients. Overexpression of NAP1 in lowly invasive NSCLC cells enhances MMP9 secretion and invasion potential, whereas NAP1 silencing in highly invasive NSCLC cells produces opposing effects in comparison. Mechanistic studies further reveal that the binding of NAP1 to the cellular chaperone heat shock protein 90 (HSP90) is required for its protein stabilization, and NAP1 plays an essential role in HSP90-mediated invasion and metastasis by provoking MMP9 activation and the epithelial-to-mesenchymal transition in NSCLC cells.

Conclusions

Our insights demonstrate the importance and functional regulation of the HSP90-NAP1 protein complex in cancer metastatic signaling, which spur new avenues to target this interaction as a novel approach to block NSCLC metastasis.

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Title: Nck-associated protein 1 associates with HSP90 to drive metastasis in human non-small-cell lung cancer
Authors: Yuanping Xiong
Leilei He
Chloe Shay
Liwei Lang
Jenni Loveless
Jieqing Yu
Ron Chemmalakuzhy
Hongqun Jiang
Manran Liu
Yong Teng
Publication date: 01-12-2019
Publisher: BioMed Central
Keywords: NSCLC
Lung Cancer
Metastasis
Lung Cancer
NSCLC
Lung Cancer
Published in: Journal of Experimental & Clinical Cancer Research / Issue 1/2019
Electronic ISSN: 1756-9966
DOI: https://doi.org/10.1186/s13046-019-1124-0

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Abstract

Background

Methods

Results

Conclusions

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