AUTHOR=Ramos Sofia , Ferreira Sandra , Fernandes Ana S. , Saraiva Nuno 

TITLE=Lysyl Oxidases Expression and Breast Cancer Progression: A Bioinformatic Analysis

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.883998

DOI=10.3389/fphar.2022.883998

ISSN=1663-9812

ABSTRACT=<p>LOX (Lysyl oxidase) and LOX like 1–4 (LOXL1–4) are amine oxidases that catalyse the cross-linking of elastin and collagen in the extracellular matrix (ECM). This activity can facilitate cell migration and the formation of metastases. Consequently, inhibition of these enzymes and, in particular of LOXL2, has been suggested as a therapeutic strategy to prevent breast cancer metastasis. Although medicinal chemistry studies have struggled to specifically inhibit LOXL2, the importance of selectivity in this context is not clear. To explore the role of each LOX in breast cancer and consequently their potential as biomarkers or therapeutic targets, a bioinformatic-based approach was followed. The expression profile of <italic>LOX</italic>s, the putative associations among mRNA expression from each <italic>LOX</italic> and clinical observations, the correlation between expression of <italic>LOX</italic> enzymes and other genes, and the association between expression of <italic>LOX</italic>s and the tumour infiltrates were assessed for breast cancer. Overall, the patient outcome and the characteristics of breast tumours with <italic>LOX</italic>, <italic>LOXL1</italic> and <italic>LOXL2</italic> upregulation is distinct from those with high expression of <italic>LOXL3</italic> and <italic>LOXL4</italic>. Additionally, the expression correlation between <italic>LOX</italic>s and other genes involved in cellular processes relevant for cancer biology, also reveals a similar trend for <italic>LOX</italic>, <italic>LOXL1</italic> and <italic>LOX2</italic>. This work further supports the relevance of LOXL2 as a breast cancer progression biomarker and therapeutic target. We speculate that while the impact of LOXL3 inhibition may vary with breast cancer subtype, the therapeutical inhibition of LOX, LOXL1 and LOXL2 but not of LOXL4 may be the most beneficial.</p>