Regulation of miR-200 family microRNAs and ZEB transcription factors in ovarian cancer: Evidence supporting a mesothelial-to-epithelial transition

Bendoraite, Ausra; Knouf, Emily C.; Garg, Kavita S.; Parkin, Rachael K.; Kroh, Evan M.; O'Briant, Kathy; Ventura, Aviva P.; Godwin, Andrew K.; Karlan, Beth Y.; Drescher, Charles W.; Urban, Nicole; Knudsen, Beatrice S.; Tewari, Muneesh

doi:10.1016/j.ygyno.2009.08.009

Cited by 176 publications

(150 citation statements)

References 47 publications

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“…Some of the first studies demonstrated that the expression of the miR-200 family was correlated with the epithelial/mesenchymal phenotype of ovarian cancer cell lines . This study as well as other studies (Bendoraite et al 2010) demonstrated that miR-200a/b/c, miR-141, and miR-429 determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressor proteins ZEB1 and ZEB2 as well as regulating oxidative stress via p38a (Mateescu et al 2011).…”

Section: Ndsupporting

confidence: 78%

The role of micro-RNAs in the female reproductive tract

Nothnick

2012

Reproduction

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Proper development and function of the female reproductive tract are essential for successful reproduction. Regulation of the differentiated functions of the organs that make up the female reproductive tract is well established to occur at multiple levels including transcription, translation, and posttranslational modifications. Micro-RNA (miRNA)-mediated posttranscriptional gene regulation has emerged as a fundamental mechanism controlling normal tissue development and function. Emerging evidence indicates that miRNAs are expressed within the organs of the female reproductive tract where they function to regulate cellular pathways necessary for proper function of these organs. In this review, the functional significance of miRNAs in the development and function of the organs of the female reproductive tract is discussed. Initial discussion focuses on the role of miRNAs in the development of the organs of the female reproductive tract highlighting recent studies that clearly demonstrate that mice with disrupted Dicer1 expression are sterile, fail to develop uterine glands, and have muted estrogen responsiveness. Next, emphasis moves to discussion on our current knowledge on the characterization of miRNA expression in each of the organs of the female reproductive tract. When possible, information is presented and discussed with respect to regulation, function, and/or functional targets of these miRNA within each specific organ of the female reproductive tract.

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Section: Ndsupporting

confidence: 78%

The role of micro-RNAs in the female reproductive tract

Nothnick

2012

Reproduction

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“…showed that PI(3) kinase contributes to TrkB signaling as well (including anoikis resistance; Douma et al, 2004), in aggregate these data suggest a model in which TrkB activates multiple pathways, some of which critically depend on Zeb1 (Figure 7). Several reports have shown a correlation between Zeb1 expression and the aggressiveness of tumors, including those of endometrial (Spoelstra et al, 2006;Singh et al, 2008), colon (Pena et al, 2005;Aigner et al, 2007b), breast (Aigner et al, 2007a), lung (Dohadwala et al, 2006), gallbladder (Adachi et al, 2009), ovarian (Bendoraite et al, 2010) and prostate origin (Graham et al, 2008). In colon cancer, Zeb1 expression is linked to loss of the basement membrane, which correlates with increased metastasis (Spaderna et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Zeb1 is required for TrkB-induced epithelial-mesenchymal transition, anoikis resistance and metastasis

Smit

Peeper

2011

Oncogene

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Anoikis (detachment-induced apoptosis) prevents the survival of cells at inappropriate sites of the body and can therefore act as a barrier to metastasis. In a functionbased genome-wide screen, we have previously identified the neurotrophic tyrosine kinase receptor TrkB as a potent suppressor of anoikis. Consistently, activated TrkB oncogenically transforms non-malignant epithelial cells and causes them to invade and produce metastatic tumors in vivo. Overexpression of activated TrkB also results in morphological transformation, resembling epithelial-mesenchymal transition (EMT). E-cadherin, an important EMT regulator, and two E-cadherin repressors, Twist and Snail, are critical for these TrkB functions. As Snail has been shown to induce Zeb1, another E-cadherin repressor, we hypothesized that Zeb1 could be a TrkB target, too. We show here that Zeb1 is required for TrkB-induced EMT in epithelial cells, as RNAi-mediated knockdown of Zeb1 reverted the morphological changes induced by TrkB. Furthermore, Zeb1 is involved in TrkB-induced anoikis resistance, migration and invasion. In vivo, knockdown of Zeb1 strongly reduced TrkB-induced metastasis. Finally, epistasis experiments showed that Zeb1 acts downstream of Twist and Snail. We conclude that Zeb1 is required for several TrkB-induced effects in vitro and in vivo, including metastasis.

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“…There are three main concepts which should be taken into consideration, 1) epithelial-mesenchymal transition (EMT) and its reversion, i.e. mesenchymal-epithelial transition [14,15], 2) secondary origin of ovarian cancer from Müllerian system [16,17] , and 3) cancer stem cells hypothesis [18].…”

Section: Disputed Origin Of the Epithelial Ovarian Cancermentioning

confidence: 99%

Ovarian cancer: Origin and factors involved in carcinogenesis with potential use in diagnosis, treatment and prognosis of the disease

Záveský

Jancárková²,

Kohoutová³

2011

neo

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Ovarian cancer representing the most lethal gynecologic malignancy escapes from the efforts to manage the disease. We reviewed the current state of the research considering three main concepts on origin of ovarian cancer including epithelialmesenchymal transition, secondary origin from Müllerian system and cancer stem cell hypothesis. Cytogenetic and molecular characteristics of ovarian cancer are focused particularly on microRNA expression studies revealing huge potential in recent years, although other transcriptomic, proteomic, epigenetic, epidemiologic and immunological factors are touched upon, too. Routine and investigated diagnostic and treatment methods are outlined and several factors revealed to be associated with prognosis of the disease. Despite the huge progress on elucidating factors involved in ovarian cancer carcinogenesis, still remains urgent need to improve both the diagnostics as well as the treatment.

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Regulation of miR-200 family microRNAs and ZEB transcription factors in ovarian cancer: Evidence supporting a mesothelial-to-epithelial transition

Cited by 176 publications

References 47 publications

The role of micro-RNAs in the female reproductive tract

The role of micro-RNAs in the female reproductive tract

Zeb1 is required for TrkB-induced epithelial-mesenchymal transition, anoikis resistance and metastasis

Ovarian cancer: Origin and factors involved in carcinogenesis with potential use in diagnosis, treatment and prognosis of the disease

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