Pro-oncogenic action of LOX-1 and its splice variant LOX-1Δ4 in breast cancer phenotypes

Pucci, Sabina; Polidoro, Chiara; Greggi, Chiara; Amati, Francesca; Morini, Elena; Murdocca, Michela; Biancolella, Michela; Orlandi, Augusto; Sangiuolo, Federica; Novelli, Giuseppe

doi:10.1038/s41419-018-1279-1

Cited by 25 publications

(24 citation statements)

References 22 publications

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“…Several studies have indicated that overexpression of COX-2, and to a lesser extent of COX-1, is directly associated with breast cancer [24][25][26]. Similar to COXs, lipoxygenase (LOX), which produces prostaglandins via a different pathway, has been found to be associated with breast cancer [27][28][29]. Taken together, overexpression of COXs and LOXs has been directly associated with breast cancer, which supports our results that mastitis increases the risk of breast cancer.…”

Section: Discussionsupporting

confidence: 89%

Risk of Breast Cancer in Women with Mastitis: A Retrospective Population-Based Cohort Study

et al. 2020

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Background and objectives: Breast cancer is a common cancer in women and has been the fourth leading cause of death in Taiwanese women. Risk factors for breast cancer include family history of breast cancer, genetic factors, and not breastfeeding. Several studies have reported an association between repeated inflammation at a young age, especially among lactating women, and cancer; however, the number of studies about the association of mastitis and breast cancer in nonlactating women is still limited. Therefore, the aim of this study was to determine the relationship between mastitis in women aged ≥40 years and breast cancer. Materials and Methods: This was a retrospective cohort study design. The data source was the Longitudinal Health Insurance Database 2010 (LHID 2010), comprising data collected by Taiwan’s National Health Insurance program. Cases of newly diagnosed mastitis in women aged ≥40 years (ICD-9-CM code = 611.0) were selected from the years 2010 to 2012. Women not diagnosed with mastitis were selected as the control group, and their data for the years 2009 to 2013 were obtained through the database. In addition, the non-mastitis group was matched 1:10 by age. Results: A total of 8634 participants were selected from the LHID 2010, which included 734 cases with mastitis and 7900 cases without mastitis. After adjustment for age, hypertension, hyperlipidemia, diabetes, hypothyroidism, and autoimmune diseases, the Cox proportional hazard model showed that patients with mastitis had a higher risk of breast cancer (aHR = 3.71, 95% CI = 1.9–7.02) compared with the non-mastitis group. The Kaplan–Meier curve also showed that women with mastitis had a higher risk of developing breast cancer. Conclusions: This study confirmed that women with mastitis have a higher risk of developing breast cancer. Therefore, women aged ≥40 years could reduce breast cancer risk by taking precautions to prevent mammary gland infection and mastitis.

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Section: Discussionsupporting

confidence: 89%

Risk of Breast Cancer in Women with Mastitis: A Retrospective Population-Based Cohort Study

et al. 2020

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“…LOX-1, a marker for atherosclerosis (2), results to be overexpressed in several types of cancer, suggesting its role at the interface of atherosclerosis, metabolic disease and cancer (3, 4, 6–8, 33).…”

Section: Discussionmentioning

confidence: 99%

Targeting LOX-1 Inhibits Colorectal Cancer Metastasis in an Animal Model

et al. 2019

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Recurrence and metastasis are the primary causes of mortality in patients with colorectal cancer (CRC), and therefore effective tools to reduce morbidity and mortality of CRC patients are necessary. LOX-1, the ox-LDL receptor, is strongly involved in inflammation, obesity, and atherosclerosis, and several studies have assessed its role in the carcinogenesis process linking ROS, metabolic disorders and cancer. We have already demonstrated in vitro that LOX-1 expression correlates to the aggressiveness of human colon cancer and its downregulation weakens the tumoral phenotype, indicating its potential function as a biomarker and a target in CRC therapy. Here we further investigate in vivo the role of LOX-1 in colon tumorigenesis by xenografting procedures, injecting nude mice both subcutaneously and intravenously with human high grade metastatic colorectal cancer cells, DLD-1, in which LOX-1 expression has been downregulated by shRNA (LOX-1RNAi cells). Histopathological and immunohistochemical evaluations have been performed on xenograft tumors. The experiments have been complemented by the analysis of the volatile compounds (VOCs) collected from the cages of injected mice and analyzed by gas-chromatography and gas sensors. After intravenous injection of LOX-1RNAi cells, we found that LOX-1 silencing influences both the engraftment of the tumor and the metastasis development, acting by angiogenesis. For the first time, we have observed that LOX-1 inhibition significantly prevents metastasis formation in injected mice and, at the same time, induces a downregulation of VEGF-A165, HIF-1α, and β-catenin whose expression is involved in cell migration and metastasis, and a variation of histone H4 acetylation pattern suggesting also a role of LOX-1 in regulating gene transcription. The analysis of the volatile compounds (VOCs) collected from the cages of injected mice has evidenced a specific profile in those xenograft mice in which metastasis originates. These findings underline the role of LOX-1 as a potential target for inhibition of tumor progression and metastasis, enhancing current therapeutic strategies against colorectal cancer.

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“…OxLDL lecithin-like receptor 1 (OLR1) is the main receptor for internalization of oxLDL. It is overexpressed in human breast cancer and positively correlates to tumor stage and grade [80]. A microarray analysis of hearts of Olr1 KO mice compared with wild-type mice showed a reduction in the expression of nuclear factor κB (NF-κB) target genes involved in cellular transformation (regulation of apoptosis, proliferation, wound healing, defense response, immune response, and cell migration) as well as an inhibition of key enzymes involved in lipogenesis.…”

Section: Low-density Lipoprotein and Breast Cancermentioning

confidence: 99%

HDL and LDL: Potential New Players in Breast Cancer Development

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Reddy

Mato

et al. 2019

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Breast cancer is the most prevalent cancer and primary cause of cancer-related mortality in women. The identification of risk factors can improve prevention of cancer, and obesity and hypercholesterolemia represent potentially modifiable breast cancer risk factors. In the present work, we review the progress to date in research on the potential role of the main cholesterol transporters, low-density and high-density lipoproteins (LDL and HDL), on breast cancer development. Although some studies have failed to find associations between lipoproteins and breast cancer, some large clinical studies have demonstrated a direct association between LDL cholesterol levels and breast cancer risk and an inverse association between HDL cholesterol and breast cancer risk. Research in breast cancer cells and experimental mouse models of breast cancer have demonstrated an important role for cholesterol and its transporters in breast cancer development. Instead of cholesterol, the cholesterol metabolite 27-hydroxycholesterol induces the proliferation of estrogen receptor-positive breast cancer cells and facilitates metastasis. Oxidative modification of the lipoproteins and HDL glycation activate different inflammation-related pathways, thereby enhancing cell proliferation and migration and inhibiting apoptosis. Cholesterol-lowering drugs and apolipoprotein A-I mimetics have emerged as potential therapeutic agents to prevent the deleterious effects of high cholesterol in breast cancer.

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Pro-oncogenic action of LOX-1 and its splice variant LOX-1Δ4 in breast cancer phenotypes

Cited by 25 publications

References 22 publications

Risk of Breast Cancer in Women with Mastitis: A Retrospective Population-Based Cohort Study

Risk of Breast Cancer in Women with Mastitis: A Retrospective Population-Based Cohort Study

Targeting LOX-1 Inhibits Colorectal Cancer Metastasis in an Animal Model

HDL and LDL: Potential New Players in Breast Cancer Development

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