Dysregulation of Lysyl Oxidase Expression in Lesions and Endometrium of Women With Endometriosis

Ruiz, Lynnette A.; Báez-Vega, Perla M.; Ruiz, Abigail; Peterse, Daniëlle; Monteiro, Janice; Bracero, Nabal; Beauchamp, Pedro J.; Fazleabas, Asgerally T.; Flores, Idhaliz

doi:10.1177/1933719115585144

Cited by 39 publications

(26 citation statements)

References 84 publications

(105 reference statements)

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“…MMP-2 promotes angiogenesis during endometriosis progression via the cyclooxygenase (COX)-2/PGE2/pAKT axis (104). The upregulation of lysyl oxidase (LOX) expression is involved in extracellular membrane degradation, invasive and metastatic potential of endometriosis (105). The disruption of epithelialstromal communication networks elicits a feed-forward loop involving endometriosis to drive inflammation, which may be relevant in diseases such as EAOC.…”

Section: Similar Epigenetic Modifications: Gene-environment Interactimentioning

confidence: 99%

Integrating modern approaches to pathogenetic concepts of malignant transformation of endometriosis

et al. 2018

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In the present study, we summarize the role of the shared and independent (epi)genetic background between endometrioid carcinoma (EC) and clear cell carcinoma (CCC), two histological subtypes of endometriosis-associated ovarian cancer (EAOC). Using the PubMed database, we conducted a literature review of various studies related to the malignant transformation of endometriosis. Both endometriosis and EAOC face potential environmental hazards, including hemoglobin (Hb), heme and free iron, which induces DNA damage and mutations. Although EC is distinguished from CCC due to different morphologies, both represent common environmental profiles and maintain the similar (epi)genomic abnormalities with multiple overlaps and share similar molecular signatures. By contrast, EAOC also has diseasespecific gene signatures corresponding with each histological subtype: Estrogen receptor promotes EC cell proliferation ('go') and hepatocyte nuclear factor-1β (HNF-1β) induces CCC cell cycle arrest ('stop') under oxidative stress conditions. This model underscores a subtype-dependent 'go or stop' dichotomy, possibly through better ability to adapt in a changing environment. It was found that cyst fluid Hb and iron concentrations were significantly lower in EAOC when compared to benign ovarian endometrioma (OE), supporting the hypothesis that the redox imbalance plays a key role in the pathogenesis of EAOC. There are at least two phases of iron carcinogenesis and tumor progression: The initial wave of iron-induced oxidative stress and DNA mutations would be followed by the second big wave of subsequent synthesis of the antioxidants, which diminishes cellular oxidative stress capacity, increases apoptosis resistance and promotes tumor initiation and progression. Special emphasis is given to novel pathophysiological concepts of malignant transformation of endometriosis.

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Section: Similar Epigenetic Modifications: Gene-environment Interactimentioning

confidence: 99%

Integrating modern approaches to pathogenetic concepts of malignant transformation of endometriosis

et al. 2018

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“…Moreover, previous studies have shown that LOX plays a crucial role in mediating proliferation, migration, and invasion by endometrial and endometriotic cells. Specifically, LOX influences the expression of genes related to fibrosis and ECM remodeling, including E-cadherin [6], which is indicative of its pro-metastatic potential. A recent study by Thomas et al [7] showed that LOX induces pre-metastatic bone lesions in breast cancer patients (especially ER– subgroup) by disrupting normal bone homeostasis.…”

Section: Introductionmentioning

confidence: 99%

Potential options for managing LOX+ ER− breast cancer patients

et al. 2016

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Overexpression of lysyl oxidase (LOX) is often observed in estrogen receptor negative (ER–) breast cancer patients with bone metastasis. In the present bioinformatics study, we observed that LOX is a prognostic factor for poor progression free survival in patients with ER– breast cancer. LOX overexpression was positively correlated with resistance to radiation, doxorubin and mitoxantrone, but negatively correlated with resistance to bisphosphonate, PARP1 inhibitors, cisplatin, trabectedin and gemcitabine. LOX overexpression was also associated with EMT and stemness of cancer cells, which leads to chemotherapeutic resistance and poor outcome in ER– patients. Although we suggest several therapeutic interventions that may help in the management of LOX+ ER– breast cancer patients, experiments to validate the function of LOX in ER– breast cancer are still needed.

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“…Our results in mouse uterus showed specific localization of Lox in the stromal cells surrounding the implanting embryos and the decidual cells during decidualization. High level of Lox expression is observed in the stromal cells in the endometrium of fertile women during WOI . The spatio‐temporally specific localization suggests the importance of Lox‐induced ECM remodeling during early pregnancy.…”

Section: Discussionmentioning

confidence: 96%

Molecular characterization of lysyl oxidase‐mediated extracellular matrix remodeling during mouse decidualization

Yan

Song

et al. 2017

FEBS Letters

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The establishment of decidualization is a prerequisite of successful pregnancy. Lysyl oxidase (Lox) is a copper-containing amine oxidase which catalyzes cross-linking of collagen and elastin in the ECM. Lox is expressed in the subluminal stroma surrounding the implanting blastocyst on day 5 of pregnancy. From days 6 to 8, the signals for Lox mRNA and protein are strongly detected in the decidual cells. The expression of Lox is under the control of estrogen via the GSK-3β/β-catenin/c-myc pathway. Dtprp is decreased by the inhibition of Lox activity. Furthermore, the inhibition of Lox activity decreases stromal cell migration and embryo adhesion. Our findings highlight the crucial role of Lox in endometrial stromal cells and deepen our understanding of decidualization.

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Dysregulation of Lysyl Oxidase Expression in Lesions and Endometrium of Women With Endometriosis

Cited by 39 publications

References 84 publications

Integrating modern approaches to pathogenetic concepts of malignant transformation of endometriosis

Integrating modern approaches to pathogenetic concepts of malignant transformation of endometriosis

Potential options for managing LOX+ ER− breast cancer patients

Molecular characterization of lysyl oxidase‐mediated extracellular matrix remodeling during mouse decidualization

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