Oncotarget

Research Papers:

LKB1 loss cooperating with BRAF V600E promotes melanoma cell invasion and migration by up-regulation MMP-2 via PI3K/Akt/mTOR pathway

Weiming Zhang, Li Yin, Guoxin Song, Xue Han, Zhiqiang Yin and Dan Luo _

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Oncotarget. 2017; 8:113847-113857. https://doi.org/10.18632/oncotarget.22943

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Abstract

Weiming Zhang1,*, Li Yin2,*, Guoxin Song1, Xue Han1, Zhiqiang Yin2 and Dan Luo2

1Department of Pathology, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China

2Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China

*These authors have contributed equally to this work

Correspondence to:

Dan Luo, email: luodanjsph@126.com

Zhiqiang Yin, email: yzq2802@sina.com

Keywords: melanoma; LKB1; BRAF; MMP-2; PI3K/mTOR

Received: February 13, 2017     Accepted: August 04, 2017     Published: December 05, 2017

ABSTRACT

The serine/threonine kinase LKB1, act as a tumor suppressor, has been reported in several sporadic cancers. However, how the loss of LKB1 promotes melanoma invasion and metastasis remains incompletely understood. In this study, we inactivated LKB1expression by RNA interference in BRAF mutation and wild type melanoma cells respectively. We found LKB1 inactivation cooperate with BRAF V600E lead to melanoma cells more aggressive by a series of experiments including wound scratch test, Transwell assay. While single alteration, either LKB1 loss or BRAF V600E, fails to enhance melanoma cells invasion ability. Mechanistically, LKB1 loss synergism with BRAF V600E resulted in the activation of the PI3K/Akt/mTOR signaling pathway and significant up-regulation expression of MMP-2. In addition, LKB1 expression in human melanoma tissues was negatively associated with MMP-2 expression in the presence of BRAF V600E. Thus, our findings indicate a probable explanation on LKB1 function as a tumor suppressor in melanoma and a new therapeutic strategy for melanoma by targeting on BRAF and LKB1 together.


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