动物造模 z-bio 2022-06-29 457

　　A study published in the journal Cancer Research by researchers at the Mayo Clinic in Florida confirms that genes that control brain growth and development are also actively involved in promoting clear cell renal cell carcinoma, the most common form of kidney cancer.

　　Their study, which revealed that the gene NPTX2 plays a crucial role in this cancer type, not only shows that NPTX2 is active in kidney cancer, but is also the first to reveal that the gene is overexpressed in any human cancer. The researchers are now looking to see if NPTX2 might play a role in other cancers.

　　We found that genes known to play a role in healthy brains are also associated with this deadliest cancer of the urinary system, we don't yet know why NPTX2 is expressed in kidney cancer, but we now know what it does in kidney cancer, and how it can contribute to the development of cancer. Because the NPTX2 gene is not expressed in normal kidney tissue, drugs aimed at targeting this protein would provide targeted therapy.

　　Lead author Christina von Roemeling et al. analyzed the genomes of nearly 100 kidney cancer patient samples, compared with genes in matched patient samples of normal kidney tissue, to determine which genes were overexpressed or underexpressed. Von Roemeling and the team then silenced the top 200 genes with changes one by one to see how those genes affected tumor growth. They found 31 genes that are important for cancer cell growth or viability, and they identified NPTX2 as a key gene for cancer survival. Co-author Dr. Derek Radisky used nine publicly available genomic datasets to search for the NPTX2 gene in kidney cancer and found it to be a closely related gene.

　　The researchers also found that the receptor GluR4, the receptor for the NPTX2 protein, was also found in kidney cancer samples. They discovered how NPTX2 and GluR4 promote cancer growth and metastasis. In kidney cancer, the overexpressed NPTX2 protein is secreted from the cell and then attaches itself to the kidney cancer cell membrane GluR4. NPTX2 causes multiple GluR4 proteins to clump together to form a channel into the cell, which allows calcium to flow in. Elevated calcium triggers multiple signaling pathways, promotes cancer cell survival by multiplying, and promotes tumor invasion and metastasis.

　　Perhaps blocking GluR4 channels can lead to cancer cell death, the investigators found that NPTX2 is expressed in all stages of kidney cancer, especially metastasis, suggesting that it plays an important role in tumorigenesis and progression. Its expression can be used as a biomarker to test which patients may benefit from NPTX2 inhibitors.