Table 2.

Selected examples of known LOX/LOXL family links with various cancers.

Breast Cancer
Lysyl oxidases associated with chemotherapy resistance in triple negative breast cancer	[99]
Stromal expression of LOXL2 is associated with tumor aggression and disease-specific mortality.	[100]
Oncostatin-M-induced ECM remodelling via upregulated LOXL2	[101]
Inhibition of LOXL4 decreased breast cancer cell proliferation, migration, and metastasis in vitro and in vivo.	[102,103]
LOXL2 promotes tumour lymph-angiogenesis and lymph node metastasis.	[104]
LOX expression is significantly higher in triple negative breast cancers versus other breast cancer subtypes.	[105]
LOXL2 involved with breast cancer metastasis to the lung	[106]
LOXL2 expression may serve as a biomarker for breast cancer and is detectable in serum and urine.	[107]
LOX and LOXL proteins are located in the stromal reaction of ductal carcinoma in situ (DCIS) breast cancer.	[108,109]
Renal Cell Cancer (RCC)
LOX and LOXL2 significantly elevated in RCC and associated with poorer overall survival (OS)	[110]
LOXL2 associated with migration, invasion and EMT transition of RCC	[111]
Primary RCC cultuure endogenously express LOX, and plays major roles in progression via activities on cellular adhesion, migration, and collagen stiffness.	[112]
Early demonstration of overexpression of LOX mRNA in RCC	[113]
Non-Small Cell Lung Cancer (NSCLC)
A novel LOX polymorphism G473A is associated with increased risk for lung cancer.	[114,115,116]
LOXL1 promotes lung cancer tumourigenicity via collagen matrix remodelling and collagen fibre alignment in vitro and in vivo.	[33]
High expression of LOX and LOXL2 mRNA and protein is associated with poor prognosis in NSCLC patients.	[117,118,119,120]
Low expression of the LOXL2 protein in adenocarcinomas is associated with a poorer N-stage, a higher pathological TNM stage and poorer differentiation.	[121]
The miR-200/ZEB1 axis drives lung cancer metastasis through LOXL2.	[122]
LOX activity is associated with increased invasion and migration of hypoxic NSCLC cells.	[123]
Reduced levels of microRNA-29a (miR-29a) in lung cancer is associated with overexpression of LOXL2 and concomitant fibrosis.	[124]
Pancreatic Cancer (PDAC)
Tumor stiffening reversion through collagen crosslinking inhibition improves T-cell migration and anti-PD-1 treatment.	[125]
LOXL2 is highly up-regulated (≥20-fold) in the PDAC secretome.	[126]
High expression of LOXL2 protein is associated with worse DFS and OS in patients with PDAC.	[127]
Increased levels of LOX, LOXL1, and LOXL2 expression in PDAC are associated with poor responses to chemotherapy by limiting drug distribution, and inhibition of LOX enhances drug efficacy.	[128,129]
In an orthotopic PDX model of PDAC, targeting LOXL2 led to accelerated tumour growth, and poorer overall survival.	[130]
Levels of LOX are a potential prognostic markers for the prognosis of pancreatic cancer patients.	[131]
Liver Cancer
Reduced levels of miR-29a in hepatocellular carcinoma (HCC) lead to elevated expression of its known targets LOX and LOXL2.	[132]
A circRNA network has been identified that activates LOX transcription in HCC.	[133]
High LOXL3 expression predicts poor outcomes for patients with HCC, and is correlated with immune infiltrates and T-cell activation.	[134]
High LOX expression is associated with an higher recurrence rate and poorer OS in patients with HCC.	[135,136]
LOXL2 is overexpressed in HCC and positively correlated with tumour grade, metastasis, and poor OS.	[137,138,139]
LOXL2 is significantly overexpressed in human HCC sera and may act as a good biomarker for HCC.	[140]
LOXL4 is upregulated in HCC tissues and associated with poor prognosis. Exosomal-mediated transfer of LOXL4 between HCC cells and human umbilical vein endothelial cells (HUVECs) promotes cell migration and angiogenesis, respectively	[141]