LKB1 Inhibits Lung Cancer Progression Through Lysyl Oxidase and Extracellular Matrix Remodeling

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2010 Oct 20

PMID 20956321

Citations 108

Authors

Yijun Gao

Qian Xiao

Huimin Ma

Li Li

Jun Liu

Yan Feng

Zhaoyuan Fang

Jing Wu

Xiangkun Han

Junhua Zhang

Yihua Sun

Gongwei Wu

Robert Padera

Haiquan Chen

Kwok-Kin Wong

Gaoxiang Ge

Hongbin Ji

Affiliations

Soon will be listed here.

Abstract

LKB1 loss-of-function mutations, observed in ∼30% of human lung adenocarcinomas, contribute significantly to lung cancer malignancy progression. We show that lysyl oxidase (LOX), negatively regulated by LKB1 through mTOR-HIF-1α signaling axis, mediates lung cancer progression. Inhibition of LOX activity dramatically alleviates lung cancer malignancy progression. Up-regulated LOX expression triggers excess collagen deposition in Lkb1-deficient lung tumors, and thereafter results in enhanced cancer cell proliferation and invasiveness through activation of β1 integrin signaling. High LOX level and activity correlate with poor prognosis and metastasis. Our findings provide evidence of how LKB1 loss of function promotes lung cancer malignancy through remodeling of extracellular matrix microenvironment, and identify LOX as a potential target for disease treatment in lung cancer patients.

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