FOXO3a modulates WNT/β-catenin signaling and suppresses epithelial-to-mesenchymal transition in prostate cancer cells

Líu, Hao; Yin, Jun; Wang, Hongsheng; Jiang, Guanmin; Deng, Min; Zhang, Ge; Bu, Xianzhang; Cai, Shaohui; Du, Jie; He, Zhiwei

doi:10.1016/j.cellsig.2015.01.001

Cited by 135 publications

(128 citation statements)

References 48 publications

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“…FOXC1 and FOXQ1 have been reported to directly bind to the promoter of E-cadherin repressors in cancer cells (14,15). FOXO3 modulates EMT indirectly through the transactivation of miRNA-34b/ c, which inhibits b-catenin expression (34). Here, we showed for the first time that FOXL2 directly regulated chemotherapyassociated metastasis and EMT in gastric cancer, and simultaneous alterations in Snail1 and ZEB2 levels were observed when FOXL2 was regulated in gastric cancer cells.…”

Section: Resultsmentioning

confidence: 54%

HMGA2–FOXL2 Axis Regulates Metastases and Epithelial-to-Mesenchymal Transition of Chemoresistant Gastric Cancer

Dong

Wang

Ren

et al. 2017

Clinical Cancer Research

121

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Purpose: Chemoresistance is the main cause of treatment failure in cancer and is associated with distant metastases and epithelial-tomesenchymal transition (EMT). This study was aimed to explore the mechanism of metastases and EMT in chemoresistant gastric cancer.Experimental Design: A key molecular pathway was identified via gene profiling and a bioinformatic analysis in a chemoresistant gastric cancer model. The roles of FOXL2, HMGA2, and ITGA2 were validated via loss-of-function and gain-of-function experiments in vitro and in an orthotopic gastric cancer animal model. The regulation of FOXL2 by HMGA2 was explored via immunoprecipitation and luciferase reporter assays. The expression of these proteins in gastric cancer tissues was examined by IHC.Results: HMGA2 and FOXL2 directly regulated the metastasis and EMT of chemoresistant gastric cancer. The interaction between HMGA2 and pRb facilitated the transactivation of FOXL2 by E2F1, and ITGA2 was the downstream effector of the HMGA2-FOXL2 pathway. HMGA2, FOXL2, and ITGA2 were associated with the TNM classification and staging of gastric cancer and were increased in metastatic lymph nodes and distant metastases. Increased HMGA2, FOXL2, and ITGA2 levels were associated with reduced overall survival periods of patients with gastric cancer.Conclusions: This study demonstrated that the transactivation of FOXL2 driven by interactions between HMGA2 and pRb might exert critical effects on the metastases and EMT of chemoresistant gastric cancer. Blocking the HMGA2-FOXL2-ITGA2 pathway could serve as a new strategy for gastric cancer treatment.

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Section: Resultsmentioning

confidence: 54%

HMGA2–FOXL2 Axis Regulates Metastases and Epithelial-to-Mesenchymal Transition of Chemoresistant Gastric Cancer

Dong

Wang

Ren

et al. 2017

Clinical Cancer Research

121

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“…Human cir-ITCH cDNA was synthesized by GeneWiz (Suzhou, China) and cloned into pcDNA3.1 (Invitrogen, CA, USA) as previously described [15, 16]. Recombinant plasmid pcDNA3.1- cir-ITCH was verified by direct sequencing.…”

Section: Methodsmentioning

confidence: 99%

“…Circular RNA-ITCH ( cir-ITCH ) shared some miRNAs binding sites with the 3′-untranslated region (UTR) of ITCH, including those for miR-7, miR-17, miR-214, miR-128, and miR-216b [7, 12, 15]. As sponge of oncogenic miR-7, miR-17, and miR-214, cir-ITCH increases the level of ITCH and thus indirectly inhibits the activation of Wnt/ β -catenin pathway; these effects finally result in the suppression of esophageal squamous cell carcinoma [16] and colorectal cancer [15]. However, there are no reported studies on the functional roles of cir-ITCH in lung cancer.…”

Section: Introductionmentioning

confidence: 99%

Circular RNA-ITCH Suppresses Lung Cancer Proliferation via Inhibiting the Wnt/β-Catenin Pathway

Wan

Zhang

Fan

et al. 2016

BioMed Research International

282

263

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As a special form of noncoding RNAs, circular RNAs (circRNAs) played important roles in regulating cancer progression mainly by functioning as miRNA sponge. While the function of circular RNA-ITCH (cir-ITCH) in lung cancer is still less reported, in this study, we firstly detected the expression of cir-ITCH in tumor tissues and paired adjacent noncancer tissues of 78 patients with lung cancer using a TaqMan-based quantitative real-time PCR (qRT-PCR). The results showed that the expression of cir-ITCH was significantly decreased in lung cancer tissues. In cellular studies, cir-ITCH was also enhanced in different lung cancer cell lines, A549 and NIC-H460. Ectopic expression of cir-ITCH markedly elevated its parental cancer-suppressive gene, ITCH, expression and inhibited proliferation of lung cancer cells. Molecular analysis further revealed that cir-ITCH acted as sponge of oncogenic miR-7 and miR-214 to enhance ITCH expression and thus suppressed the activation of Wnt/β-catenin signaling. Altogether, our results suggested that cir-ITCH may play an inhibitory role in lung cancer progression by enhancing its parental gene, ITCH, expression.

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“…Via EMT, epithelial cells dissolve intercellular connections and acquire mesenchymal properties and metastasize to the native or distant sites. Once cancer cells seed the metastatic site, a mesenchymal to epithelial transition (MET) occurs, inducing colonization and growth of the metastatic foci with re-expression of cell adhesion molecule E-cadherin, facilitating tumor cells to seed in the metastatic sites [34][35][36][37][38][39][40]. E-cadherin re-expression accompanied by a partial MET in the metastatic sites increases post-extravasation survival of the cancer cells and resistance to multi-drugs [35,37].…”

Section: Epithelial-mesenchymal Transitions (Emt)mentioning

confidence: 99%

Potential molecular, cellular and microenvironmental mechanism of sorafenib resistance in hepatocellular carcinoma

et al. 2015

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FOXO3a modulates WNT/β-catenin signaling and suppresses epithelial-to-mesenchymal transition in prostate cancer cells

Cited by 135 publications

References 48 publications

HMGA2–FOXL2 Axis Regulates Metastases and Epithelial-to-Mesenchymal Transition of Chemoresistant Gastric Cancer

HMGA2–FOXL2 Axis Regulates Metastases and Epithelial-to-Mesenchymal Transition of Chemoresistant Gastric Cancer

Circular RNA-ITCH Suppresses Lung Cancer Proliferation via Inhibiting the Wnt/β-Catenin Pathway

Potential molecular, cellular and microenvironmental mechanism of sorafenib resistance in hepatocellular carcinoma

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