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1.
Cell Death Dis ; 15(7): 514, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39025841

RESUMO

Prostate cancer exhibits high prevalence and accounts for a high number of cancer-related deaths. The discovery and characterization of molecular determinants of aggressive prostate cancer represents an active area of research. The Immediate Early Response (IER) family of genes, which regulate Protein Phosphatase 2A (PP2A) activity, has emerged among the factors that influence cancer biology. Here, we show that the less studied member of this family, Immediate Early Response 5 like (IER5L), is upregulated in aggressive prostate cancer. Interestingly, the upregulation of IER5L expression exhibits a robust association with metastatic disease in prostate and is recapitulated in other cancer types. In line with this observation, IER5L silencing reduces foci formation, migration and invasion ability in a variety of human and murine prostate cancer cell lines. In vivo, using zebrafish and immunocompromised mouse models, we demonstrate that IER5L-silencing reduces prostate cancer tumor growth, dissemination, and metastasis. Mechanistically, we characterize the transcriptomic and proteomic landscapes of IER5L-silenced cells. This approach allowed us to identify DNA replication and monomeric G protein regulators as downstream programs of IER5L through a pathway that is consistent with the regulation of PP2A. In sum, we report the alteration of IER5L in prostate cancer and beyond and provide biological and molecular evidence of its contribution to tumor aggressiveness.


Assuntos
Progressão da Doença , Neoplasias da Próstata , Proteína Fosfatase 2 , Masculino , Neoplasias da Próstata/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Humanos , Proteína Fosfatase 2/metabolismo , Proteína Fosfatase 2/genética , Animais , Camundongos , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Peixe-Zebra , Movimento Celular/genética , Proliferação de Células
2.
Proc Natl Acad Sci U S A ; 120(52): e2310797120, 2023 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-38113260

RESUMO

We demonstrate geostationary satellite monitoring of large transient methane point sources with the US Geostationary Operational Environmental Satellites (GOES). GOES provides continuous 5- to 10-min coverage of the Americas at 1 to 2 km nadir pixel resolution in two shortwave infrared spectral bands from which large methane plumes can be retrieved. We track the full evolution of an extreme methane release from the El Encino-La Laguna natural gas pipeline in Durango, Mexico on 12 May 2019. The release lasted 3 h at a variable rate of 260 to 550 metric tons of methane per hour and totaled 1,130 to 1,380 metric tons. We report several other detections of transient point sources from oil/gas infrastructure, from which we infer a detection limit of 10 to 100 t h-1. Our results show that extreme releases of methane can last less than an hour, as from deliberate venting, and would thus be difficult to identify and quantify with low-Earth orbit satellites.

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