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IKKα Promotes the Progression and Metastasis of Non-Small Cell Lung Cancer Independently of its Subcellular Localization.

Abstract：

:Lung cancer is the leading worldwide cause of cancer mortality, however, neither curative treatments nor substantial prolonged survival has been achieved, highlighting the need for investigating new proteins responsible for its development and progression. IKKα is an essential protein for cell survival and differentiation, which expression is enhanced in human non-small cell lung cancer (NSCLC) and correlates with poor patient survival, appearing as a relevant molecule in lung cancer progression. However, there are not conclusive results about its role in this type of cancer. We have recently found that IKKα performs different functions and activates different signaling pathways depending on its nuclear or cytoplasmic localization in tumor epidermal cells. In this work, we have studied the involvement of IKKα in lung cancer progression through the generation of lung cancer cell lines expressing exogenous IKKα either in the nucleus or in the cytoplasm. We demonstrate that IKKα signaling promotes increased cell malignancy of NSCLC cells as well as lung tumor progression and metastasis in either subcellular localization, through activation of common protumoral proteins, such as Erk, p38 and mTor. But, additionally, we found that depending on its subcellular localization, IKKα has non-overlapping roles in the activation of other different pathways known for their key implication in lung cancer progression: while cytoplasmic IKKα increases EGFR and NF-κB activities in lung tumor cells, nuclear IKKα causes lung tumor progression through c-Myc, Smad2/3 and Snail activation. These results suggest that IKKα may be a promising target for intervention in human NSCLC.

journal_name

Comput Struct Biotechnol J

journal_title

Computational and structural biotechnology journal

authors

Page A,Ortega A,Alameda JP,Navarro M,Paramio JM,Saiz-Pardo M,Almeida EI,Hernández P,Fernández-Aceñero MJ,García-Fernández RA,Casanova ML

doi

10.1016/j.csbj.2019.02.003

subject

Has Abstract

pub_date

2019-02-07 00:00:00

pages

251-262

issn

2001-0370

pii

S2001-0370(18)30257-5

journal_volume

pub_type

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IKKα Promotes the Progression and Metastasis of Non-Small Cell Lung Cancer Independently of its Subcellular Localization.