Good news! Cancer is history (soon)!
"... Publishing in Cell Reports, researchers identified a long-overlooked autophagy regulator that stops breast cancers from crossing tissue boundaries.3 By studying variation in this gene, scientists may one day leverage it to predict metastases in cancer patients. ...
Out of 171 autophagy-regulating genes, they identified a few dozen that curbed metastasis. In their absence, tumor cells spread to the lung, an organ to which this cancer type doesn’t typically venture. The gene that codes for p47 protein produced the biggest difference when depleted, suggesting that it plays a key role in curbing breast cancer metastasis. “Previously, it was unknown that it could affect cancer,” ..."
Out of 171 autophagy-regulating genes, they identified a few dozen that curbed metastasis. In their absence, tumor cells spread to the lung, an organ to which this cancer type doesn’t typically venture. The gene that codes for p47 protein produced the biggest difference when depleted, suggesting that it plays a key role in curbing breast cancer metastasis. “Previously, it was unknown that it could affect cancer,” ..."
From the highlights and abstract:
"Highlights
• In vivo CRISPR screen reveals p47 as a suppressor of HER2+ breast cancer metastasis
• p47 depletion reduces NEMO endosomal trafficking and increases NF-κB signaling
• p47 ablation impairs lysosome repair and autophagy flux and increases metastasis
• Lower p47 expression correlates to increased metastasis in human breast cancer
Summary
Autophagy is a conserved cellular process, and its dysfunction is implicated in cancer and other diseases. Here, we employ an in vivo CRISPR screen targeting genes implicated in the regulation of autophagy to identify the Nsfl1c gene encoding p47 as a suppressor of human epidermal growth factor receptor 2 (HER2)+ breast cancer metastasis. p47 ablation specifically increases metastasis without promoting primary mammary tumor growth. Analysis of human breast cancer patient databases and tissue samples indicates a correlation of lower p47 expression levels with metastasis and decreased survival. Mechanistic studies show that p47 functions in the repair of lysosomal damage for autophagy flux and in the endosomal trafficking of nuclear factor κB essential modulator for lysosomal degradation to promote metastasis. Our results demonstrate a role and mechanisms of p47 in the regulation of breast cancer metastasis. They highlight the potential to exploit p47 as a suppressor of metastasis through multiple pathways in HER2+ breast cancer cells."
Graphical abstract:
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