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Cystic fibrosis transmembrane conductance regulator—emerging regulator of cancer

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Abstract

Mutations of cystic fibrosis transmembrane conductance regulator (CFTR) cause cystic fibrosis, the most common life-limiting recessive genetic disease among Caucasians. CFTR mutations have also been linked to increased risk of various cancers but remained controversial for a long time. Recent studies have begun to reveal that CFTR is not merely an ion channel but also an important regulator of cancer development and progression with multiple signaling pathways identified. In this review, we will first present clinical findings showing the correlation of genetic mutations or aberrant expression of CFTR with cancer incidence in multiple cancers. We will then focus on the roles of CFTR in fundamental cellular processes including transformation, survival, proliferation, migration, invasion and epithelial–mesenchymal transition in cancer cells, highlighting the signaling pathways involved. Finally, the association of CFTR expression levels with patient prognosis, and the potential of CFTR as a cancer prognosis indicator in human malignancies will be discussed.

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Abbreviations

ABC:

Adenosine triphosphate (ATP)-binding cassette

CF:

Cystic fibrosis

CFTR:

Cystic fibrosis transmembrane conductance regulator

EMT:

Epithelium–mesenchymal transition

Hsp:

Heat shock protein

HIF-1α:

Hypoxia induced factor-1α

MDR:

Multidrug resistance

NF-κB:

Nuclear factor kappa-light-chain-enhancer of activated B cells

NPC:

Nasopharyngeal carcinoma

NSCLC:

Non-small cell lung cancer

PTC:

Papillary thyroid cancer

SCC:

Squamous cell carcinoma

SNPs:

Single nucleotide polymorphisms

TGF-β:

Transforming growth factor-β

uPA:

Urokinase-type plasminogen activator

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Funding

The work was supported in parts by National 973 Project (2013CB967404, 2013CB967401, 2013CB967403), Research Grant Council of Hong Kong (CUHK 466413, CUHK14119516), National Natural Science Foundation of China (81571390), the Focused Investment Scheme of the Chinese University of Hong Kong and L.K.S Foundation.

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  1. Xiaohua Jiang and Hsiao Chang Chan contributed equally to this work.

Authors and Affiliations

  1. Faculty of Medicine, Epithelial Cell Biology Research Center, School of Biomedical Sciences, The Chinese University of Hong Kong, Sha Tin, Hong Kong SAR, People’s Republic of China

    Jieting Zhang, Yan Wang, Xiaohua Jiang & Hsiao Chang Chan

  2. Key Laboratory for Regenerative Medicine of the Ministry of Education of China, Faculty of Medicine, School of Biomedical Sciences, The Chinese University of Hong Kong, Sha Tin, Hong Kong SAR, People’s Republic of China

    Jieting Zhang, Yan Wang, Xiaohua Jiang & Hsiao Chang Chan

  3. School of Biomedical Sciences Core Laboratory, Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, People’s Republic of China

    Jieting Zhang, Yan Wang, Xiaohua Jiang & Hsiao Chang Chan

  4. Sichuan University-The Chinese University of Hong Kong Joint Laboratory for Reproductive Medicine, West China Second University Hospital, Chengdu, People’s Republic of China

    Hsiao Chang Chan

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  1. Jieting Zhang
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JZ and YW have contributed to data collection and manuscript written. Prof. XJ and Prof. HCC have contributed to write and finalize the paper.

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Correspondence to Xiaohua Jiang or Hsiao Chang Chan.

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Zhang, J., Wang, Y., Jiang, X. et al. Cystic fibrosis transmembrane conductance regulator—emerging regulator of cancer. Cell. Mol. Life Sci. 75, 1737–1756 (2018). https://doi.org/10.1007/s00018-018-2755-6

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  • DOI: https://doi.org/10.1007/s00018-018-2755-6

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