Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1522282 (EMT)
 2,868 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cell migration and invasion are highly regulated processes involved in both physiological and pathological conditions. Here we show that autophagy modulation regulates the migration and invasion capabilities of glioblastoma (GBM) cells. We observed that during autophagy occurrence, obtained by nutrient deprivation or by pharmacological inhibition of the mTOR complexes, GBM migration and chemokine-mediated invasion were both impaired. We also observed that SNAIL and SLUG, two master regulators of the epithelial-mesenchymal transition (EMT process), were down-regulated upon autophagy stimulation and, as a consequence, we found a transcriptional and translational up-regulation of N- and R-cadherins. Conversely, in BECLIN 1-silenced GBM cells, an increased migration capability and an up-regulation of SNAIL and SLUG was observed, with a resulting decrease in N- and R-cadherin mRNAs. ATG5 and ATG7 down-regulation also resulted in an increased migration and invasion of GBM cells combined to an up-regulation of the two EMT regulators. Finally, experiments performed in primary GBM cells from patients largely confirmed the results obtained in established cell cultures. Overall, our results indicate that autophagy modulation triggers a molecular switch from a mesenchymal phenotype to an epithelial-like one in GBM cellular models. Since the aggressiveness and lethality of GBM is defined by local invasion and resistance to chemotherapy, we believe that our evidence provides a further rationale for including autophagy/mTOR-based targets in the current therapeutical regimen of GBM patients.
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PMID:Autophagy induction impairs migration and invasion by reversing EMT in glioblastoma cells. 2602 8

Estrogen receptor (ER) antagonist, tamoxifen has been universally used for the treatment of the ER-positive breast cancer; however, the inevitable emergence of resistance to tamoxifen obstructs the successful treatment of this cancer. So, there is an immediate requirement for the search of a novel therapeutic target for treatment of this cancer. Acquired tamoxifen-resistant breast cancer cell lines MCF-7 (MCF-7/TAM-R) and T47D (T47D/TAM-R) showed higher apoptotic resistance accompanied by induction of pro-survival autophagy compared to their parental cells. Besides, tamoxifen resistance was associated with reduced production of ATP and with overexpression of glycolytic pathways, leading to induced autophagy to meet the energy demand. Further, our study revealed that LDHA; one of the key molecules of glycolysis in association with Beclin-1 induced pro-survival autophagy in tamoxifen-resistant breast cancer. Mechanistically, pharmacological and genetic inhibition of LDHA reduced the pro-survival autophagy, with the restoration of apoptosis and reverting back the EMT like phenomena noticed in tamoxifen-resistant breast cancer. In total, targeting LDHA opened a novel strategy to interrupt autophagy and tamoxifen resistance in breast cancer.
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PMID:Lactate dehydrogenase A regulates autophagy and tamoxifen resistance in breast cancer. 3087 2

Xanthoangelol (XAG), a prenylated chalcone isolated from the Japanese herb Angelica keiskei Koidzumi, has been reported to exhibit antineoplastic properties. However, the specific anti-tumor activity of XAG in human hepatocellular carcinoma (HCC), and the relevant mechanisms are not known. Herein, we evaluated the effect of XAG against HCC in vitro and in vivo. Although XAG treatment did not significantly reduce the viability of the Hep3B and Huh7 cell lines, it suppressed cell migration, invasion, and EMT. This anti-metastatic effect of XAG was due to induction of autophagy, because treatment with the autophagy inhibitor 3-methyadenine (3-MA) or knockdown of the pro-autophagy Beclin-1 effectively abrogated the XAG-induced suppression of metastasis. Mechanistically, XAG induced autophagy via activation of the AMPK/mTOR signaling pathway, and XAG treatment dramatically increased the expression of p-AMPK while decreasing p-mTOR expression. In addition, blocking AMPK/mTOR axis with compound C abrogated the autophagy-mediated inhibition of metastasis. The murine model of HCC metastasis also showed that XAG effectively reduced the number of metastatic pulmonary nodules. Taken together, our results revealed that autophagy via the activation of AMPK/mTOR pathway is essential for the anti-metastatic effect of XAG against HCC. These findings not only contribute to our understanding of the anti-tumor activity of XAG but also provide a basis for its clinical application in HCC. Before this study, evidence of XAG on HCC was purely anecdotal; present study provides the first comprehensive assessments of XAG on HCC metastasis and investigates its underlying mechanism. Results suggest that XAG exerts anti-metastatic properties against HCC through inducing autophagy which is mediated by the activation of AMPK/mTOR signaling pathway. This research extends our knowledge about the antineoplastic properties of XAG and suggests that induction autophagy may represent future treatment strategies for metastatic HCC.
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PMID:Autophagy induction by xanthoangelol exhibits anti-metastatic activities in hepatocellular carcinoma. 3088 49

Papillary thyroid carcinoma (PTC) is the most common cancer of the endocrine system, which is usually associated with a favorable therapeutic response and prognosis. However, metastatic spreading occurs in around 5% of the PTC patients. Identification of molecular markers could early predict the metastatic potential, which is essential for reducing the patient's overtreatment. Baculoviral IAP Repeat Containing 7 (BIRC7) is an inhibitor of apoptosis protein (IAP) family gene that is known to be linked to tumor progression, but its role in the setting of PTC metastasis remains unknown. This study, therefore, aims to explore the role of BIRC7 in the metastasis and autophagy of PTC and elucidate its underlying molecular mechanisms. BIRC7 expression was assessed in fresh samples of human PTC and normal tissues via qRT-PCR and immunohistochemistry. In addition, BIRC7 was overexpressed and silenced in PTC cell lines followed by transmission electron microscopy, western blotting, immunofluorescence microscopy, wound healing and invasion assays. We further explored the relevance of BIRC7 in vivo using a tumor xenograft model. Our results demonstrated that BIRC7 plays a pro-invasive role in PTC. BIRC7 expression is significantly upregulated in PTC compared with matched thyroid normal tissues. In addition, we found that BIRC7 knockdown induced a significant reduction in PTC cell EMT and metastasis in vitro and in vivo, while overexpression of BIRC7 markedly enhanced PTC cell migration and invasion. Moreover, our data showed that BIRC7 was able to suppress autophagy through modulating the expression of ATG5 and BECN1, and that this suppression is responsible for BIRC7 silence induced suppression of EMT and metastasis of PTC cell. We further found that targeting both BIRC7 and mTOR enhances autophagy in PTC cells and to achieve synergistic antimetastatic efficacy in vitro and in vivo. These findings indicate that the suppression of autophagy by BIRC7 drives the invasion and metastasis of PTC cells, thus suggesting that the activation of autophagy may inhibit metastasis of PTC with high BIRC7 expression.
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PMID:BIRC7 promotes epithelial-mesenchymal transition and metastasis in papillary thyroid carcinoma through restraining autophagy. 3206 54