Lysyl oxidase family members in urological tumorigenesis and fibrosis.

Tao Li,Feng Qin,Jiuhong Yuan,Liang Gao,Changjing Wu,Qiang Wei

doi:10.18632/oncotarget.24948

Tao Li, Feng Qin + Show 4 more

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https://doi.org/10.18632/oncotarget.24948

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Abstract

Lysyl oxidase (LOX) is an extracellular copper-dependent monoamine oxidase that catalyzes crosslinking of soluble collagen and elastin into insoluble, mature fibers. Lysyl oxidase-like proteins (LOXL), LOX isozymes with partial structural homology, exhibit similar catalytic activities. This review summarizes recent findings describing the roles of LOX family members in urological cancers and fibrosis. LOX/LOXL play key roles in extracellular matrix stability and integrity, which is essential for normal female pelvic floor function. LOX/LOXL inhibition may reverse kidney fibrosis and ischemic priapism. LOX and LOXL2 reportedly promote kidney carcinoma tumorigenesis, while LOX, LOXL1 and LOXL4 suppress bladder cancer growth. Multiple studies agree that the LOX propeptide may suppress tumor growth, but the role of LOX in prostate cancer remains controversial. Further studies are needed to clarify the exact effects and mechanism of LOX/LOXL on urological malignancies.

Highlights

Lysyl oxidase (LOX) is a copper-dependent monoamine oxidase in the extracellular matrix (ECM) [1]
This review summarizes recent findings describing the roles of LOX family members in urological cancers and fibrosis
LOXL2 overexpression was associated with higher clear cell renal cell carcinoma (ccRCC) pathological stages, and upregulated integrins-α5/ β1, which enhanced cancer cell survival, invasion, and metastasis via protease- and proteasome-dependent mechanisms [31]

Summary

Introduction

Lysyl oxidase (LOX) is a copper-dependent monoamine oxidase in the extracellular matrix (ECM) [1]. LOX and LOXL2 reportedly promote kidney carcinoma tumorigenesis, while LOX, LOXL1 and LOXL4 suppress bladder cancer growth. LOXL2 overexpression was correlated with more aggressive breast cancer [14, 15], and primary gastric tumor invasion, lymph node metastasis, and reduced patient survival. These studies suggest that LOX/LOXL promote cancer progression.

Results

Conclusion