Good news! Cancer is history (soon)!
"Researchers have discovered a gene that helps pancreatic and breast cancers spread in mice. Gstt1 produces glutathione S-transferase, an enzyme that encourages cancer cells to secrete the protein fibronectin. This protein helps cancer cells bind to the extracellular matrix and start a new life in a tissue far away from the primary tumour. When Gstt1 was silenced in human cell lines and mice, fewer cancer cells were disseminated. This study provides “a strong rationale for the targeting of Gstt1 to treat metastatic disease”, write the researchers."
From the 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 Gstt1high population is highly metastatic and retains slow-cycling phenotypes, epithelial–mesenchymal transition features and DTC characteristics compared to the Gstt1low 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."
The glutathione S-transferase Gstt1 drives survival and dissemination in metastases (no public access, but article above contains link to PDF file)
Fig. 1 A shRNA screen targeting metastatic genes identifies Gstt1 as a regulator of metastasis
Fig. 2 Gstt1 is required for metastatic maintenance and dissemination
No comments:
Post a Comment