Abstract
Emerging evidence has implicated a pivotal role for lysyl oxidase (LOX) in cancer progression and metastasis. Whilst the majority of work has focused on the extracellular matrix cross-linking role of LOX, the exact function of intracellular LOX localisation remains unclear. In this study, we analysed the LOX expression patterns in the nuclei of rectal cancer patient samples and determined the clinical significance of this expression. Nuclear LOX expression was significantly increased in patient lymph node metastases compared to their primary tumours. High nuclear LOX expression in tumours was correlated with a high rate of distant metastasis and increased recurrence. Multivariable analysis showed that high nuclear LOX expression was also correlated with poor overall survival and disease free survival. Furthermore, we are the first to identify LOX enzyme isoforms (50 kDa and 32 kDa) within the nucleus of colon cancer cell lines by confocal microscopy and Western blot. Our results show a powerful link between nuclear LOX expression in tumours and patient survival, and offer a promising prognostic biomarker for rectal cancer patients.
Highlights
Colorectal cancer (CRC) is the third most common cancer worldwide with approximately 694,000 estimated deaths
The results show that cytoplasmic lysyl oxidase (LOX) is associated with diseased tissue
We have shown that nuclear LOX expression was significantly increased in lymph node metastases compared to primary tumours, and that this high nuclear expression was correlated with distance metastasis
Summary
Colorectal cancer (CRC) is the third most common cancer worldwide with approximately 694,000 estimated deaths. This makes it the fourth most common cause of cancer death [1]. Lysyl oxidase (LOX) is a secreted copper-dependent amine oxidase, which catalyses the crosslinking of collagens and elastin in the extracellular matrix (ECM) and is essential for embryonic development and would healing. It is synthesized as a 50-kDa proenzyme, secreted, and processed into a 32-kDa mature, active enzyme and an 18-kDa propeptide (LOX-PP) [4]. In addition to an ECM remodeling role, LOX has been shown to function intracellularly, regulating both cell signalling and gene expression [5, 6]
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