A splicing variant of Merlin promotes metastasis in hepatocellular carcinoma

Zai-Li Luo, Shu-Qun Cheng, Jie Shi, Hui-Lu Zhang, Cun-Zhen Zhang, Hai-Yang Chen, Bi-Jun Qiu, Liang Tang, Cong-Li Hu, Hong-Yang Wang () and Zhong Li ()
Additional contact information
Zai-Li Luo: International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiiary Surgery Institute/Hospital, The Second Military Medical University
Shu-Qun Cheng: Eastern Hepatobiliary Surgery Institute/Hospital, The Second Military Medical University
Jie Shi: Eastern Hepatobiliary Surgery Institute/Hospital, The Second Military Medical University
Hui-Lu Zhang: International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiiary Surgery Institute/Hospital, The Second Military Medical University
Cun-Zhen Zhang: Eastern Hepatobiliary Surgery Institute/Hospital, The Second Military Medical University
Hai-Yang Chen: International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiiary Surgery Institute/Hospital, The Second Military Medical University
Bi-Jun Qiu: Renji Hospital, School of Medicine, Shanghai Jiao Tong University
Liang Tang: International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiiary Surgery Institute/Hospital, The Second Military Medical University
Cong-Li Hu: International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiiary Surgery Institute/Hospital, The Second Military Medical University
Hong-Yang Wang: International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiiary Surgery Institute/Hospital, The Second Military Medical University
Zhong Li: Cancer Institute, The First Affiliated Hospital of Henan University of Science and Technology

Nature Communications, 2015, vol. 6, issue 1, 1-11

Abstract: Abstract Merlin, which is encoded by the tumour suppressor gene Nf2, plays a crucial role in tumorigenesis and metastasis. However, little is known about the functional importance of Merlin splicing forms. In this study, we show that Merlin is present at low levels in human hepatocellular carcinoma (HCC), particularly in metastatic tumours, where it is associated with a poor prognosis. Surprisingly, a splicing variant of Merlin that lacks exons 2, 3 and 4 (Δ2–4Merlin) is amplified in HCC and portal vein tumour thrombus (PVTT) specimens and in the CSQT2 cell line derived from PVTT. Our studies show that Δ2–4Merlin interferes with the capacity of wild-type Merlin to bind β-catenin and ERM, and it is expressed in the cytoplasm rather than at the cell surface. Furthermore, Δ2–4Merlin overexpression increases the expression levels of β-catenin and stemness-related genes, induces the epithelium–mesenchymal-transition phenotype promoting cell migration in vitro and the formation of lung metastasis in vivo. Our results indicate that the Δ2–4Merlin variant disrupts the normal function of Merlin and promotes tumour metastasis.

Date: 2015
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms9457 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9457

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms9457

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().