AI Article Synopsis

  • Plexins are important receptors for semaphorins that influence cell behavior, such as movement and invasion, and are linked to cancer progression.
  • A study analyzed the plexin genes in melanomas and pancreatic ductal adenocarcinomas, finding that PLXNA4 was amplified in melanomas while PDACs showed losses in various plexin genes.
  • Mutations were identified in several plexin genes, including PLXNA4 and PLXNB3, suggesting that these genetic changes can impair their function and may play a role in the advancement of cancer.

Article Abstract

Plexins are transmembrane high-affinity receptors for semaphorins, regulating cell guidance, motility, and invasion. Functional evidences implicate semaphorin signals in cancer progression and metastasis. Yet, it is largely unknown whether plexin genes are genetically altered in human tumors. We performed a comprehensive gene copy analysis and mutational profiling of all nine members of the plexin gene family (plexinome), in melanomas and pancreatic ductal adenocarcinomas (PDACs), which are characterized by high metastatic potential and poor prognosis. Gene copy analysis detected amplification of PLXNA4 in melanomas, whereas copy number losses of multiple plexin genes were seen in PDACs. Somatic mutations were detected in PLXNA4, PLXNB3, and PLXNC1; providing the first evidence that these plexins are mutated in human cancer. Functional assays in cellular models revealed that some of these missense mutations result in loss of plexin function. For instance, c.1613G>A, p.R538H mutation in the extracellular domain of PLXNB3 prevented binding of the ligand Sema5A. Moreover, although PLXNA4 signaling can inhibit tumor cell migration, the mutated c.5206C>T, p.H1736Y allele had lost this activity. Our study is the first systematic analysis of the "plexinome" in human tumors, and indicates that multiple mutated plexins may be involved in cancer progression.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2989154PMC
http://dx.doi.org/10.1002/humu.21017DOI Listing

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