Ninety percent of cancer deaths are due to the spread of cancer, not complications from the original tumor.
Rockefeller UniversityDec 9 2024 Thus, for over 50 years now, scientists have been on a quest to identify which malignant mutations within the tumor allow rogue cells to break away from the primary tumor and travel through the bloodstream and lymphatic system to metastasize throughout the body.
Metastasis we believe is, at least in part, a hereditary disorder. We have been so focused on the cancer cells, the 'seeds', that we've ignored the germline-;'the soil'. It's now clear that focusing on the soil is critical." Root of the problem Although scientists have rigorously investigated metastasis for decades, extensive genomic sequencing of metastatic tumors have come up empty.
A common variant of the PCSK9 gene immediately caught their attention. Present in the germlines of 70 percent of white women, this gene variant was associated with reduced breast cancer survival. And when the team engineered mice with the relevant variant form of human PCSK9, the rate of metastasis increased. Colleagues at Lund University in Sweden further validated these results with an analysis of a large Scandinavian cohort of early-stage breast cancer patients.
Digging deeper The study, which was funded by the Hess Family Foundation and the National Cancer Institute, also sheds light on how the PCSK9 variant drives metastasis. By degrading the LRP1 receptor on cancer cells, the variant appears to unleash a cascade of gene activation ideal for metastatic initiation. Interestingly, the lab's prior work on melanoma found that the APOE alleles that promote or suppress metastasis also act on LRP1.
Cancer Genetic Metastasis Cell DNA Gene Genetics Germline Laboratory Lymphatic System Malignant Melanoma Receptor Research Tumor
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