MAPK Kinase 3 Is a Tumor Suppressor with Reduced Copy Number in Breast Cancer

MacNeil, Adam J.; Jiao, Shunchang; McEachern, Lori A.; Yang, Yong; Dennis, Amanda; Yu, Haiming; Xu, Zhaolin; Marshall, Jean S.; Lin, Tong‐Jun

doi:10.1158/0008-5472.can-13-1310

Cited by 27 publications

(27 citation statements)

References 49 publications

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“…MAP2K3 pathways play a critical role in carcinogenesis. MAP2K3 has been shown to suppress the growth of breast cancer cells (46) and alterations in its pathway are frequent in UBC (47). Finally, the protein encoded by CD3G is part of the T-cell receptor-CD3 complex.…”

Section: Discussionmentioning

confidence: 99%

Inflammatory-Related Genetic Variants in Non–Muscle-Invasive Bladder Cancer Prognosis: A Multimarker Bayesian Assessment

Masson-Lecomte

Maturana

Goddard

et al. 2016

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: Increasing evidence points to the role of tumor immunologic environment on urothelial bladder cancer prognosis. This effect might be partly dependent on the host genetic context. We evaluated the association of SNPs in inflammationrelated genes with non-muscle-invasive bladder cancer (NMIBC) risk-of-recurrence and risk-of-progression.Methods: We considered 822 NMIBC included in the SBC/ EPICURO Study followed-up >10 years. We selected 1,679 SNPs belonging to 251 inflammatory genes. The association of SNPs with risk-of-recurrence and risk-of-progression was assessed using Cox regression single-marker (SMM) and multimarker methods (MMM) Bayes A and Bayesian LASSO. Discriminative abilities of the models were calculated using the c index and validated with bootstrap cross-validation procedures.Results: While no SNP was found to be associated with risk-ofrecurrence using SMM, three SNPs in TNIP1, CD5, and JAK3

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Section: Discussionmentioning

confidence: 99%

Inflammatory-Related Genetic Variants in Non–Muscle-Invasive Bladder Cancer Prognosis: A Multimarker Bayesian Assessment

Masson-Lecomte

Maturana

Goddard

et al. 2016

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…Pathological staging was performed according to the international staging system for nonsmall cell lung carcinoma . The detailed procedures for immunohistochemical analysis were performed as previously described . Briefly, antigen retrieval was performed by heating the samples in a steamer for 10 minutes with 10 mM sodium citrate (pH = 6.0).…”

Section: Methodsmentioning

confidence: 99%

Targeting the Wnt-Regulatory Protein CTNNBIP1 by microRNA-214 Enhances the Stemness and Self-Renewal of Cancer Stem-Like Cells in Lung Adenocarcinomas

Chen

Cheng

et al. 2015

Stem Cells

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A novel hypothesis in cancer biology proposes that cancer growth is driven by cancer stem-like cells (CSLCs), also called tumor-initiating cells, which can self-renew and differentiate into multilineage progeny in a fashion similar to stem cells. However, the impact and underlying mechanisms of this process in lung adenocarcinoma (LAC) remain to be elucidated. Here, we report that microRNA-214 (miR-214) contributes to cell self-renewal by directly targeting catenin beta interacting protein 1 (CTNNBIP1), a member of the Wnt signaling pathway. We demonstrate that miR-214 overexpression enhances stem-like properties in LAC cells and that miR-214 shows increased expression in CSLCs derived from primary tumor tissue and from two LAC cell lines (A549 and NCI-H1650). Strikingly, downregulation of miR-214 expression in CSLCs resulted in a significant decrease in spheroid formation and the expression of the stem-cell markers Nanog, Oct-4, and Sox-2. Finally, CTNNBIP1 was identified as a target of miR-214. miR-214 expression in LAC was negatively correlated with CTNNBIP1 expression and positively correlated with differentiated cellular states. Moreover, CTNNBIP1 expression correlated with longer overall survival in LAC patients. This study reveals that miR-214 plays a critical role in CSLC self-renewal and stemness by targeting CTNNBIP1. The identification of this functional miR-214-CTNNBIP1 interaction that regulates self-renewal in CSLCs has the potential to direct the development of novel therapeutic strategies for LAC. STEM CELLS 2015;33:3423-3436 SIGNIFICANCE STATEMENTThis study is the first to investigate and identify the role of miR-214 in lung adenocarcinoma (LAC) from a perspective of CSLC regulation. We show that miR-214 inhibits CTNNBIP1 expression and thereby illuminate the mechanism of Wnt/b-catenin signal activation in CSLCs in LAC. Finally, we investigate the significance of CTNNBIP1 in clinical patients and find that CTNNBIP1 expression is positively correlated with differentiated cancer-cell grades and predicted prognosis in patients with LAC. The identification of the miR-214-CTNNBIP1 pathway that regulates selfrenewal and stemness in CSLCs has potential to facilitate the development of novel therapeutic strategies for the patients with LAC.

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“…IHC and semiquantitative optical analysis was performed as described previously (24) and seen in Supplementary Materials and Methods. Primary antibodies to CD68, CD163, and IL17A were purchased from Abcam, ERa and TET1 from Sigma-Aldrich, and 5-hmC from Active Motif.…”

Section: Endometrial Sample Collection and Ihcmentioning

confidence: 99%

Infiltrating Macrophages Induce ERα Expression through an IL17A-mediated Epigenetic Mechanism to Sensitize Endometrial Cancer Cells to Estrogen

et al. 2016

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Persistent unopposed estrogen stimulation is a central oncogenic mechanism driving the formation of type I endometrial cancer. Recent epidemiologic and clinical studies of endometrial cancer have also revealed a role for insulin resistance, clinically manifested by chronic inflammation. However, the role of inflammation in estrogen-driven endometrial cancer is not well characterized. In this study, we investigated the association between infiltrating macrophages and estrogen sensitivity in endometrial cancer. Evaluating tissue samples and serum from patients with precancerous lesions or endometrial cancer, we found that tissue macrophage infiltration, but not serum estradiol levels, correlated positively with endometrial cancer development. Furthermore, IL4/IL13-induced CD68 þ CD163 þ macrophages enhanced the proliferative effects of estradiol in endometrial cancer cells by upregulating estrogen receptor alpha (ERa), but not ERb. Mechanistic investigations revealed that CD68 þ CD163 þ macrophages secreted cytokines, such as IL17A, that upregulated ERa expression through TET1-mediated epigenetic modulation of the ERa gene. Overall, our findings show how cytokines produced by infiltrating macrophages in the endometrial microenvironment can induce epigenetic upregulation of ERa expression, which in turn sensitizes endometrial cells to estrogen stimulation. The concept that inflammation-induced estrogen sensitivity in the endometrium acts as a driver of type I endometrial cancer has implications for infiltrating macrophages as a prognostic biomarker of progression in this disease setting.

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MAPK Kinase 3 Is a Tumor Suppressor with Reduced Copy Number in Breast Cancer

Cited by 27 publications

References 49 publications

Inflammatory-Related Genetic Variants in Non–Muscle-Invasive Bladder Cancer Prognosis: A Multimarker Bayesian Assessment

Inflammatory-Related Genetic Variants in Non–Muscle-Invasive Bladder Cancer Prognosis: A Multimarker Bayesian Assessment

Targeting the Wnt-Regulatory Protein CTNNBIP1 by microRNA-214 Enhances the Stemness and Self-Renewal of Cancer Stem-Like Cells in Lung Adenocarcinomas

Infiltrating Macrophages Induce ERα Expression through an IL17A-mediated Epigenetic Mechanism to Sensitize Endometrial Cancer Cells to Estrogen

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