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The glutathione S-transferase Gstt1 drives survival and dissemination in metastases.

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Nature cell biology 📖 저널 OA 65% 2024: 0/2 OA 2025: 3/7 OA 2026: 10/11 OA 2024~2026 2024 Vol.26(6) p. 975-990
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Ferrer CM, Cho HM, Boon R, Bernasocchi T, Wong LP, Cetinbas M

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Identifying the adaptive mechanisms of metastatic cancer cells remains an elusive question in the treatment of metastatic disease, particularly in pancreatic cancer (pancreatic adenocarcinoma, PDA).

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APA Ferrer CM, Cho HM, et al. (2024). The glutathione S-transferase Gstt1 drives survival and dissemination in metastases.. Nature cell biology, 26(6), 975-990. https://doi.org/10.1038/s41556-024-01426-7
MLA Ferrer CM, et al.. "The glutathione S-transferase Gstt1 drives survival and dissemination in metastases.." Nature cell biology, vol. 26, no. 6, 2024, pp. 975-990.
PMID 38862786 ↗

Abstract

Identifying the adaptive mechanisms of metastatic cancer cells remains an elusive question in the treatment of metastatic disease, particularly in pancreatic cancer (pancreatic adenocarcinoma, PDA). A loss-of-function shRNA targeted screen in metastatic-derived cells identified Gstt1, a member of the glutathione S-transferase superfamily, as uniquely required for dissemination and metastasis, but dispensable for primary tumour growth. Gstt1 is expressed in latent disseminated tumour cells (DTCs), is retained within a subpopulation of slow-cycling cells within existing metastases, and its inhibition leads to complete regression of macrometastatic tumours. This distinct Gstt1 population is highly metastatic and retains slow-cycling phenotypes, epithelial-mesenchymal transition features and DTC characteristics compared to the Gstt1 population. Mechanistic studies indicate that in this subset of cancer cells, Gstt1 maintains metastases by binding and glutathione-modifying intracellular fibronectin, in turn promoting its secretion and deposition into the metastatic microenvironment. We identified Gstt1 as a mediator of metastasis, highlighting the importance of heterogeneity and its influence on the metastatic tumour microenvironment.

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