IndraLab

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"Our results reveal a novel route of transendothelial migration for uveal melanoma cells, and they provide insight into the mechanism by which loss of BAP1 promotes metastasis."
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"26 The exact mechanism (s) by which loss of BAP1 mediates primary uveal melanoma metastasis is currently being investigated."
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"19 However, GNA11 mutations are also more common in tumors involving the ciliary body, which is an independent risk factor for metastasis, and in tumors with mutations in the metastasis suppressor BAP1 (Breast cancer 1, early onset (BRCA1)-associated protein 1) (see below), so it remains possible or even likely that the association between GNA11 and metastasis is not causal."
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"XREF_BIBR, XREF_BIBR The precise molecular explanation for why loss of BAP1 leads to metastasis in UM remains unclear."
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"BAP1 promotes progenitor cell differentiation into melanocytes by increasing MITF expression and BAP1 loss may promote metastasis in UM by remodeling the epigenome to resemble that of stem-like migratory neural crest cells."
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"Differential expression of the tumor suppressor BAP-1, growth factor receptor IGF-1R, and immune checkpoints IDO and TIGIT could contribute to the relative over- and underrepresentation of cell types at different stages from normal choroidal tissue to metastasis."
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"XREF_BIBR, XREF_BIBR The precise reason why loss of BAP1 promotes uveal melanoma progression and metastasis remains unclear and is the subject of intense investigation."
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"These studies could also lead to context-selective discovery of novel therapeutic strategies and understanding whether BAP1 loss promotes metastasis."
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"We find that this process requires VCAM mediated adhesion between UM cells and ECs and that loss of the metastasis suppressor BAP1 enhances TEM."
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"In more than 40% of UM cases, BAP1 loss leads to a stem-like state, affecting melanocyte differentiation and possibly driving metastasis [14,73,74,75]."
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"The strong association between BAP1 and HIF1α might determine why BAP1 loss increases the risk of metastasis in certain cancer types such UM."
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"BAP1 was assumed to be a tumour suppressor, since the majority of BAP1 mutations are deletion or inactivating mutations and loss or downregulation of BAP1 can accelerate tumour development and metasta[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
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"There was a low transcript number for BRCA1 associated protein 1 (BAP1), which when highly expressed suppresses metastasis [XREF_BIBR]."
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"Knockdown of BAP1 in TNBC cells inhibited tumorigenesis and metastasis, which could be partially rescued by restoration of KLF5 expression, suggesting that KLF5 mediates, at least in part, the breast cancer promoting function of BAP1 [XREF_BIBR]."
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"This mechanism could help explain the suppressive tumor immune microenvironment that is characteristic of BAP1-mutant uveal melanomas, and it suggests that BAP1 loss may lead to metastasis at least in part by facilitating immune escape."
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"While we and others have extensively investigated the downstream effects of BAP1 loss in UM cells [5,6,7], the mechanism by which BAP1 loss leads to metastasis remains unclear.Despite the increasingly effective management of primary UM, there has been no corresponding improvement in patient survival [8], due to a propensity for early micrometastasis and immune escape [9]."
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"However, the specific mechanisms by which BAP1 loss contributes to UM progression and metastasis remain largely unknown.Among the many binding partners of BAP1 is additional sex combs‐like transcriptional regulator 2 (ASXL2)."
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"Inactivation of BAP1 is the single most consistent mutation associated with metastatic death in UM [4,42], and yet it remains unclear how BAP1 loss promotes metastasis."
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"Given this interplay between the liver's lipid‐rich microenvironment and the role of fatty acid metabolism in ferroptosis, we hypothesize that BAP1 loss contributes to the successful metastasis of UM through unique management of the lipid‐rich liver microenvironment, thus providing insights to UM's hepatic organotropism.Understanding the interactions between UM cells and the hepatic microenvironment is essential for developing novel treatment approaches."
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"Consequently, BAP1 loss may promote metastasis at least in part by allowing tumor cells to evade the patient’s immune response."
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"BAP1-inactivated UMs are at a high risk of metastasis [13]."
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"Uveal melanoma metastatic disease has a complex development: the loss of both BAP1 alleles with mutations and chromosome 3 deletion and/or chr8q gain could drive the formation of different metastases that, after colonization of the liver, can spread to different organs."
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"Finally, to elucidate the mechanism by which BAP1 suppresses invasion and metastasis in LAC cells, we analyzed the expression levels of metastasis related proteins in transfected H1299 cells and H1650 cells using IB, respectively."
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"It will be important to elucidate how this effect of BAP1 loss promotes metastasis and how to reverse this effect therapeutically."
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"Loss of nuclear but not cytoplasmic BAP1 protein enhanced HCC metastasis."
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"The association between BAP1 loss and presence of metastases further supports this mutation as a marker of disease aggressiveness and underscores the clinical importance of BAP1 in future therapeutic development."
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"Of note, knockdown of BAP1 promoted intrahepatic tumor metastasis, with both BAP1 knockdown groups (shBAP1#1 and shBAP1#3) showing more frequent irregular tumor borders with invasion into the adjacent liver parenchyma, more frequent tumor microsatellite formation and venous invasion (Fig. 3C, D)."
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"The authors concluded that loss of BAP1 might increase susceptibility to uveal melanoma metastasis and serve as a valuable therapeutic target."
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"Prompted by these transcriptomic findings, we wished to explore further the possibility that BAP1 inhibits metastasis of uveal melanoma cells by maintaining their differentiated state and impeding their reversion to a stem like state."
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"Consistently, the knockdown of BAP1 promoted intrahepatic metastasis in HepG2 cells in vivo.Subsequently, with RNA sequencing on stable BAP1-knockdown HepG2 cells, RHOJ was identified among the gene targets that were downregulated upon BAP1 knockdown."
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"Uveal melanoma (UM) with BAP1 inactivating mutations has a high risk of metastasis, but the mechanism behind BAP1 deficiency driving UM metastasis is unknown."
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