title: Aberrant Splicing in Cancer: Mediators of Malignant Progression through an Imperfect Splice Program Shift.
abstract: Although the efforts to understand the genetic basis of cancer allowed advances in diagnosis and therapy, little is known about other molecular bases. Splicing is a key event in gene expression, controlling the excision of introns decoded inside genes and being responsible for 80% of the proteome amplification through events of alternative splicing. Growing data from the last decade point to deregulation of splicing events as crucial in carcinogenesis and tumor progression. Several alterations in splicing events were observed in cancer, caused by either missexpression of or detrimental mutations in some splicing factors, and appear to be critical in carcinogenesis and key events during tumor progression. Notwithstanding, it is difficult to determine whether it is a cause or consequence of cancer and/or tumorigenesis. Most reviews focus on the generated isoforms of deregulated splicing pattern, while others mainly summarize deregulated splicing factors observed in cancer. In this review, events associated with carcinogenesis and tumor progression mainly, and epithelial-to-mesenchymal transition, which is also implicated in alternative splicing regulation, will be progressively discussed in the light of a new perspective, suggesting that splicing deregulation mediates cell reprogramming in tumor progression by an imperfect shift of the splice program.
authors: Laboratório de Osteoimunologia e Imunologia dos Tumores, Instituto de Ciências Biomédicas (ICBIM), Universidade Federal de Uberlândia (UFU), Uberlândia, Brazil.
authors: Felipe Andrés Cordero
authors: FA
authors: Luz
authors: Paula Cristina
authors: PC
authors: Brígido
authors: Alberto Silva
authors: AS
authors: Moraes
authors: Marcelo José Barbosa
authors: MJ
authors: Silva
mesh_terms: D017398:Alternative Splicing; D063646:Carcinogenesis / Q000235:genetics*; D018450:Disease Progression; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology