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Query: UMLS:C1522282 (EMT)
 2,868 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Regulation of metastasis continues to remain enigmatic despite our improved understanding of cancer. Identification of microRNAs associated with metastasis in the recent past has provided a new hope. Here, we show how microRNA-101 (miR-101) regulates two independent processes of cellular metastasis by targeting pro-metastatic upstream regulatory transcription factors, ZEB1 and ZEB2, and downstream effector-actin modulators, RHOA and RAC1, providing a single target for therapeutic intervention. Further, we depict how down-regulation of miR-101 by extracellular signal-regulated kinase-2 (ERK2) is vital for MAP kinase pathway induced cellular migration and mesenchymal transition. Importantly, EKR2 induced expression of ZEB1 seems essential for down-regulation of miR-101-1 and induction of EMT. Given the role of EMT in metastasis, we also observe a significant correlation between miR-101 expression and lymph node metastasis; and identify the ERK2-ZEB1-miR-101-1 pathway active in breast cancer tissues, with an apparent clinicopathological implication.
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PMID:ERK2-ZEB1-miR-101-1 axis contributes to epithelial-mesenchymal transition and cell migration in cancer. 2810 9

Purpose: TIAM2 (T-cell lymphoma invasion and metastasis 2), a RAC1 guanine nucleotide exchange factor, plays crucial roles in human cancer cells. Its homolog, TIAM1, has been reported to promote the migration and invasion of cancer cells through regulating the functions of cancer associated fibroblasts (CAFs). However, the functions of TIAM2 in CAFs have not been investigated. In this study, we explored how fibroblast TIAM2 influences the migration and invasion of lung cancer cells. Methods: We cultured primary lung CAFs and adjacent normal lung fibroblasts (NFs) from 12 non-small cell lung cancer (NSCLC) patients. RT-PCR and western blot were used to compare TIAM2 levels between CAFs and NFs. Two co-culture systems were designed, in which cancer cells were directly co-cultured with fibroblasts and indirectly co-cultured with conditional medium (CM) from fibroblasts. Subsequently, the wound healing and transwell tests were conducted to assess the migration and invasion ability of fibroblasts and co-cultured cancer cells. Finally, cytokine antibody arrays were used to screen differentially secreted cytokines in the CM. Results: The expression levels of TIAM2 were significantly higher in CAFs than NFs, and TIAM2-silenced fibroblasts showed decreased migration and invasion ability. In the direct co-culture system, the migration and invasion of cancer cells were retarded when co-culturing with TIAM2-silenced fibroblasts, and the expression levels of EMT-related genes also changed in cancer cells. Decreased migration and invasion of cancer cells were also observed when culturing with the CM from TIAM2-silenced fibroblasts. In addition, the cytokine antibody arrays revealed that Osteoprotegerin (OPG) was significantly decreased in the CM of TIAM2-silenced fibroblasts. This result suggested that OPG might be one of the main cytokines contributing to the migration and invasion of cancer cells in co-culture systems. Conclusion: Our results suggest that fibroblast TIAM2 promotes the invasion and migration of lung cancer cell, and OPG might be one of the main cytokines contributing to this pro-cancer process.
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PMID:The Fibroblast TIAM2 Promotes Lung Cancer Cell Invasion and Metastasis. 3120 45

The molecular heterogeneity of renal cell carcinoma (RCC) complicates the therapeutic interventions for advanced metastatic disease and thus its management remains a significant challenge. This study investigates the role of the lncRNA CDKN2B-AS1 and miR-141-3p interactions in the progression and metastasis of kidney cancer. Human renal cancer cell lines (ACHN and Caki1), normal RPTEC cells, tissue cohorts, and a series of in vitro assays and in vivo mouse model were used for this study. An overexpression of CDKN2B-AS1 was observed in RCC compared to normal samples in TCGA and our in-house SFVAMC tissue cohorts. Reciprocally, we observed reduced expression of miR-141 in RCC compared to normal in the same cohorts. CDKN2B-AS1 shares regulatory miR-141 binding sites with CCND1 and CCND2 genes. Direct interactions of CDKN2B-AS1/miR-141/Cyclin D1-D2 were confirmed by RNA immunoprecipitation and luciferase reporter assays indicating that CDKN2B-AS1/miR-141/Cyclin D1-D2 acts as a ceRNA network in RCC. Functionally, attenuation of CDKN2B-AS1 and/or overexpression of miR-141 inhibited proliferation, clonogenicity, migration/invasion, induced apoptosis in vitro and suppressed tumor growth in xenograft mouse model. Further, overexpression of CDKN2B-AS1 is positively correlated with poor overall survival of RCC patients. Expression of miR-141 also robustly discriminated malignant from non-malignant tissues and its inhibition in normal RPTEC cells induced pro-cancerous characteristics. CDKN2B-AS1 attenuation or miR-141 overexpression decreased CCND1/CCND2 expression, resulting in reduced RAC1/pPXN that are involved in migration, invasion and epithelial-mesenchymal transition. This study, for the first time, deciphered the role of CDKN2B-AS1/miR-141/Cyclin D axis in RCC and highlights this network as a promising therapeutic target for the regulation of EMT driven metastasis in RCC.
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PMID:LncRNA CDKN2B-AS1/miR-141/cyclin D network regulates tumor progression and metastasis of renal cell carcinoma. 3281 66