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UCHL1 activates Neoplasm Metastasis. 57 / 61
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"The vitro experiments showed that over-expression of UCHL1 in osteosarcoma cancer cells promoted cell growth and metastasis, and inhibited cell apoptosis."
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"We focused on metastasis as we already determined that UCHL1 induced the expression of metastasis related genes, such as MMP2 and MMP9 (XREF_FIG and XREF_SUPPLEMENTARY)."
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"Hypermethylation of UCHL1 promotes cancer metastasis and downregulates CTTN degradation; however, it remains unclear how these CTTN ubiquitination PTMs relate to lung cell function or disease [59,60,61]."
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"UCHL1 has been shown to increase metastasis through deubiquitination and stabilization of HIF-1alpha, a central protein in tumor angiogenesis [XREF_BIBR]."
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"Ubiquitin C-terminal hydrolase-L1 (UCH-L1) has been shown to increase the stability of HIF-1α as a deubiquitinating enzyme and promote distant tumor metastases under hypoxic conditions in breast and lung cancers (34)."
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"For example, UCH-L1, according to its deubiquitination activity, inhibits the progression of malignant tumors such as NPC (67), breast cancer (26) and HCC (25) by activating p53 signaling, but promotes metastasis of gastric cancer cells by upregulating Akt and Erk1/2 signaling, and metastasis of breast and lung cancer cells by upregulating HIF-1α activity (68,69)."
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"UCH-L1 promotes the metastasis of gastric cancer cells by up-regulating protein kinase B (Akt) and extracellular signal-regulated kinases (ERK1/2), and by constructing a mouse model of lung metastasis, it was found that upregulation of hypoxia-inducible factor-1α (HIF-1α) activity promoted the metastasis of breast cancer cells and lung cancer cells [33,34]."
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"Functionally , we observed that UCHL1 promoted breast cancer migration , extravasation and metastasis both in zebrafish and mice xenograft models ."
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"UCHL1 is a key promoter of cell invasion and metastasis in small cell lung cancer but not necessarily required for cell viability or proliferation [XREF_BIBR, XREF_BIBR]."
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"UCHL1 promotes proliferation and metastasis in head and neck squamous cell carcinoma and could be a potential therapeutic target."
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"Although our results point to a pivotal role for UCHL1 in stimulating breast cancer extravasation by regulating TGFbeta signaling , we do not preclude that UCHL1 may also promote invasion and metastasis by targeting other signaling proteins ."
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"Correction: Zhao et al. Hypermethylation of UCHL1 Promotes Metastasis of Nasopharyngeal Carcinoma by Suppressing Degradation of Cortactin (CTTN)."
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"In the most aggressive triple-negative breast cancer [loss of estrogen receptor (ER), progesterone receptor and HER2 expression], overexpression of UCH-L1 promotes TGF-β signaling-induced metastasis by inhibiting degradation of the TGF-β type I receptor and its downstream effector molecule SMAD2 (29)."
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"We used an inhibitor of HIF-1, YC-1, and a plasmid expressing shRNA for HIF-1alpha, shHIF-1alpha, to directly examine the involvement of HIF-1alpha in the formation of pulmonary metastasis enhanced by UCHL1."
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"The de-ubiquitinase UCHL1 promotes gastric cancer metastasis via the Akt and Erk1/2 pathways."
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"UCHL1 expression supports breast and melanoma metastasis to lungs; inhibition of metastasis is achieved by a UCH-L1 inhibitor, LDN57444."
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"In conclusion, UCHL1 was confirmed to increase cell viability and proliferation as well as metastasis potential by stabilizing HIF‐1α to increase HIF‐1 activity in the spheroid 3D culture system.4 DISCUSSION."
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"Inhibition of UCHL1 reduced the incidence of bone metastases (3 of 7 mice) in mice bearing NEPC compared with those treated with vehicle (6 of 7 mice) (Figures 7C and 7E)."
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"(h) UCHL1: UCHL1 enhances breast cancer migration, extravasation, and metastasis in zebrafish and mouse xenograft models."
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"These studies suggest that UCH-L1 promotes cancer cell metastasis."
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"In lung adenocarcinoma , UCHL1 promotes tumor migration , invasion , and metastasis by inhibiting apoptosis and has an important impact on the clinical drug treatment of lung adenocarcinoma ."
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"Additionally, UCHL1 expression led to increased metastasis and tumor phenotype whereas its depletion showed anti-tumor effects in a lung cancer cell line [196]."
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"Furthermore, UCH-L1 was found to promote prostate cancer metastasis via EMT induction (82)."
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"UCH-L1 has been suggested to promote metastasis in colorectal, lung, and prostate cancer cells [XREF_BIBR, XREF_BIBR, XREF_BIBR]."
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"UCHL1 (Ubiquitin C-terminal hydrolase-L1) has previously been shown to reverse ubiquitylation of HIF-1α and promote metastasis in a HIF-1-dependent manner ."
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"Furthermore, a study reported that UCH-L1 may support the development of distant metastasis in endometrial cancer (99)."
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"Subsequently, it has been established that UCH-L1 overexpression further enhances metastasis or invasiveness of cells by altering cancer cell morphology and regulating the Akt signaling pathway (85)."
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"In gastric cancer and lymphoma, the promotion of cancer metastasis caused by UCH-L1 via the PI3 K/Akt signaling pathway has been studied (Hussain et al. 2010; Gu et al. 2015)."
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"Together, these data imply that UCH-L1 promotes cancer cell metastasis via beta-catenin-induced EMT (XREF_FIG)."
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"To confirm that UCH-L1 promotes pulmonary metastasis in vivo by altering H 2 O 2 levels in the invasive cells, we examined whether UCH-L1-induced ROS generation is blocked by Adv-catalase infection in a MOI dependent manner (10-50 MOI) in vitro."
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"UCH-L1 promotes cancer metastasis in prostate cancer cells through EMT induction."
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"We demonstrated that UCHL1 re-expression promoted the proliferation, migration and metastasis potential of HCT8 cells both in vitro and in vivo."
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"These results suggest that UCH-L1 does not affect cell growth and proliferation in prostate cancer cells.In non-small lung cancer cells, UCH-L1 increases cancer cell invasion and metastasis by changin[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"The exosomes secreted by ADSCs with UCHL1 knockdown significantly downregulated CD206, HDAC6, STAT3, and PD-L1 in vivo and in vitro, indicating that ADSCs-Exos mediate immune escape of TNBC cells by transporting UCHL1.Targeted inhibition of UCHL1 has been shown to enhance the efficacy of endocrine therapy against TNBC, and reduce the migration and metastasis of tumor cells [45]."
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"The authors investigated whether UCHL1 promotes breast cancer metastasis by overexpressing UCHL1 in mCherry MDA-MB-231 cells, which are UCHL1-low, and knocking down UCHL1 in mCherry MDA-MB-436 cells, which are UCHL1-high, and injecting these cells into zebrafish embryos, showing that UCHL1 overexpression or knockdown provokes a stronger or weaker metastatic phenotype, respectively, compared to untransfected control cells [54]."
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"The potential role for UCHL1 in promoting breast cancer invasion and metastasis was further supported in a murine breast cancer xenograft model, where UCHL1 overexpressing groups exhibited increased metastasis compared to UCHL1 knockdown groups.To explore the mechanism of action by which UCHL1 promotes breast cancer metastasis, Liu et al. [54] investigated UCHL1 depletion in epithelial–mesenchymal transition (EMT), which has previously been shown to play an important role in breast cancer metastasis [55]."
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"Consistent with the other results, UCH-L1 C90S did not increase the cell migration and invasion of RWPE1 cells in all assays.These results support the idea that the migratory and invasive behavior of [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"Sijia Liu et al. reported that UCHL1 enhances the process of breast cancer metastasis triggered by TGF-β signaling by safeguarding the TGF-β I receptor and SMAD2 from ubiquitination [14]."
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"Ubiquitin carboxyl terminal hydrolase L1 ( UCHL1 ) could abrogate VHL-mediated ubiquitylation of HIF-1alpha and promote metastasis in murine models of pulmonary metastasis [ 79 ] ."
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"The de-ubiquitinase UCHL1 promotes gastric cancer metastasis via the Akt and Erk1/2 pathways."
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"In the present study, we found that UCH-L1 promotes prostate cancer cell invasion and metastasis by reducing cell–cell adhesion and EMT induction."
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"Functional assays revealed that UCHL1 enhanced the development and metastasis of ccRCC."
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"Functionally , UCHL1 promoted metastasis in zebrafish and murine breast cancer xenograft models ."
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"UCHL1 is associated with HIF-1 and distant metastasis in cancer patients, suggesting that UCHL1 may promote metastasis through HIF."
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"XREF_BIBR UCHL1 has recently also been shown to promote cancer metastasis in prostate cancer cells."
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"Most of the cancer studies on UCHL1 have revealed that overexpression and promoter methylation of UCHL1 are key reasons for UCHL1 mediated metastasis."
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"UCH-L1 promotes cancer metastasis in prostate cancer cells through EMT induction."
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"Loss of UCHL1 significantly decreases tumor growth and metastasis."
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"In addition, UCHL1 overexpression promotes cancer cell migration and metastasis in NEPC and SCLC."
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"Considering the recently established functional role of extracellular vesicles (ECV) in cancer progression, we suggest that specific inhibition of C-terminal farnesylation of UCH-L1 may reduce invasion and metastasis of EBV associated LMP1 positive metastatic carcinomas."
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"UCH-L1 promotes cancer metastasis in prostate cancer cells through EMT induction."
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"On the other hand, UCHL1 acts as an oncogenic factor via PI3K/Akt, MAPK/Erk, and other signaling pathways to promote the development, invasion, and metastasis of breast cancer as well as NSCLC, lymphoma, osteosarcoma, and neuroblastoma [147]."
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"The aberrant expression of UCHL1 was shown to promote distant tumour metastasis via the activation of HIF-1."
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"Altogether , the mice and zebrafish results confirm that UCHL1 promotes breast cancer invasion and metastasis ."
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"UCHL1 has been shown to promote metastasis via the activation of HIF-1 and its overexpression also correlates with poor prognosis in patients with breast and lung cancers [XREF_BIBR]."
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"In lung adenocarcinoma, UCHL1 promotes tumor migration, invasion, and metastasis by inhibiting apoptosis and has an important impact on the clinical drug treatment of lung adenocarcinoma."
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"We propose that C-terminal farnesylation of UCH-L1 facilitates LMP1 loading in exosomes and might promote tumor invasion and metastasis through modulating the cancer microenvironment."
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