Constitutively Activated Stat3 Induces Tumorigenesis and Enhances Cell Motility of Prostate Epithelial Cells through Integrin β6

Azare, Janeen; Leslie, Kenneth; Al‐Ahmadie, Hikmat; Gerald, William L.; Weinreb, Paul H.; Violette, Shelia M.; Bromberg, Jacqueline

doi:10.1128/mcb.02404-06

Cited by 139 publications

(125 citation statements)

References 59 publications

(71 reference statements)

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“…In a previous study, a constitutive active mutant version of Stat3 (Stat3-C) was created by substituting two cysteine residues in the C-terminal loop of the SH2 domain of Stat3, thereby producing a mutant which spontaneously dimerizes upon formation of disulfide bonds, thus binding DNA to activate transcription (Bromberg et al, 1999). Moreover, the Stat3-C molecule had been demonstrated to function as constitutive transcriptional activator of Stat3 target genes in several studies (Shen et al, 2001;Niu et al, 2002;Leslie et al, 2006;Azare et al, 2007). We have generated ES cells and mice with a targeted insertion of this Stat3-C cDNA preceded by a loxP-flanked transcriptional stop cassette into the ubiquitously expressed ROSA26 locus (Fig.…”

Section: Resultsmentioning

confidence: 99%

Enhanced Stat3 Activation in POMC Neurons Provokes Negative Feedback Inhibition of Leptin and InsulinSignaling in Obesity

et al. 2009

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Section: Resultsmentioning

confidence: 99%

Enhanced Stat3 Activation in POMC Neurons Provokes Negative Feedback Inhibition of Leptin and InsulinSignaling in Obesity

et al. 2009

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“…5,[37][38][39] It has also recently been shown that Stat3 activation through Ras signaling pathway was required for EMT in salivary epithelial cells, 40 and ectopic expression of Stat3C decreased the E-cadherin level in prostate epithelial cells. 41 Concomitant with transient reduction of the let-7 level after exposure to OSM, the expression of HMGA2 was instantly upregulated, accompanied by an increase in the levels of mesenchymal markers. The expression of the let-7 family members in human is barely detectable in embryonic stages but upregulated at the end of embryonic development.…”

Section: Discussionmentioning

confidence: 99%

Stat3-coordinated Lin-28–let-7–HMGA2 and miR-200–ZEB1 circuits initiate and maintain oncostatin M-driven epithelial–mesenchymal transition

Guo¹,

Chen²,

Shi³

et al. 2013

Oncogene

178

164

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Inflammation can act as a crucial mediator of epithelial-to-mesenchymal transition (EMT). In this study, we show that oncostatin M (OSM) is expressed in an autocrine/paracrine fashion in invasive breast carcinoma. OSM stimulation promotes spontaneous lung metastasis of MCF-7 xenografts in nude mice. A conspicuous epigenetic transition was induced by OSM stimulation not only in breast cancer cell lines but also in MCF-7 xenografts in nude mice. The expression of miR-200 and let-7 family members in response to OSM stimulation was downregulated in a signal transducer and activator of transcription factor 3 (Stat3)-dependent manner, resulting in comprehensive alterations of the transcription factors and oncoproteins targeted by these microRNAs. Inhibition of Stat3 activation or the ectopic expression of let-7 and miR-200 effectively reversed the mesenchymal phenotype of breast cancer cells. Stat3 promotes the transcription of Lin-28 by directly binding to the Lin-28 promoter, resulting in the repression of let-7 expression and concomitant upregulation of the let-7 target, high-mobility group A protein 2 (HMGA2). Knock down of HMGA2 significantly impairs OSM-driven EMT. Our data indicate that downregulation of let-7 and miR-200 levels initiates and maintains OSM-induced EMT phenotypes, and HMGA2 acts as a master switch of OSM-induced EMT. These findings highlight the importance of Stat3-coordinated Lin-28B-let-7-HMGA2 and miR-200-ZEB1 circuits in the cytokine-mediated phenotypic reprogramming of breast cancer cells.

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“…After injury, remaining epithelial cells migrate and differentiate/redifferentiate to restore the normal pattern of ciliated and nonciliated cells lining the airways. The role of STAT3 in cell migration has been demonstrated in a number of experimental models (see reviews 12,[31][32][33][34]35 ). STAT3 affects cell motility through both transcriptional and non-transcriptional pathways.…”

Section: Gp130-stat3 Signaling Promotes Cell Migrationmentioning

confidence: 99%

GP130-STAT3 Regulates Epithelial Cell Migration and Is Required for Repair of the Bronchiolar Epithelium

Kida

Mucenski

Thitoff

et al. 2008

The American Journal of Pathology

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Following injury, bronchiolar cells undergo rapid squamous metaplasia, followed by proliferation and re-establishment of the complex columnar epithelium that is characteristic of the normal airway. Mechanisms that regulate the repair of bronchiolar epithelium are of considerable relevance for understanding the pathogenesis of both acute and chronic lung diseases associated with airway remodeling. This study was designed to identify the role of the GP130-STAT3 signaling pathway during repair of the bronchiolar epithelium. STAT3 ( The respiratory epithelium is recurrently subject to injury by pathogens, particles, and toxicants. Following extensive bronchiolar injury, remaining cells undergo squamous metaplasia to maintain the epithelial barrier. Thereafter, epithelial cell proliferation and differentiation restore the normal populations of ciliated and nonciliated cells lining the bronchioles. Since acute and chronic airway injuries are associated with many pulmonary diseases, the mechanisms and cellular processes regulating repair of the respiratory epithelium are of considerable interest. Repair of the bronchiolar epithelium has been studied using various agents to cause epithelial cell injury, including naphthalene, respiratory pathogens, and inhaled toxicants (see review 1 ). Naphthalene has been used to selectively kill nonciliated bronchiolar cells in the mouse lung in vivo.2-4 Within 24 hours after naphthalene exposure, Clara cells are sloughed from the bronchiolar surface. Remaining cells, consisting primarily of ciliated cells and nonciliated, naphthalene-resistant cells, undergo squamous metaplasia and spread to maintain the epithelial lining. Dynamic changes in cell shape are accompanied by the expression of a number of transcription factors and cellular markers that are also associated with the differentiation of respiratory epithelial cells during

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Constitutively Activated Stat3 Induces Tumorigenesis and Enhances Cell Motility of Prostate Epithelial Cells through Integrin β6

Cited by 139 publications

References 59 publications

Enhanced Stat3 Activation in POMC Neurons Provokes Negative Feedback Inhibition of Leptin and InsulinSignaling in Obesity

Enhanced Stat3 Activation in POMC Neurons Provokes Negative Feedback Inhibition of Leptin and InsulinSignaling in Obesity

Stat3-coordinated Lin-28–let-7–HMGA2 and miR-200–ZEB1 circuits initiate and maintain oncostatin M-driven epithelial–mesenchymal transition

GP130-STAT3 Regulates Epithelial Cell Migration and Is Required for Repair of the Bronchiolar Epithelium

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