Aberrant splicing of the DMP1-ARF-MDM2-p53 pathway in cancer

International Journal of Cancer. Journal International Du Cancer
Kazushi Inoue, Elizabeth A Fry

Abstract

Alternative splicing (AS) of mRNA precursors is a ubiquitous mechanism for generating numerous transcripts with different activities from one genomic locus in mammalian cells. The gene products from a single locus can thus have similar, dominant-negative or even opposing functions. Aberrant AS has been found in cancer to express proteins that promote cell growth, local invasion and metastasis. This review will focus on the aberrant splicing of tumor suppressor/oncogenes that belong to the DMP1-ARF-MDM2-p53 pathway. Our recent study shows that the DMP1 locus generates both tumor-suppressive DMP1α (p53-dependent) and oncogenic DMP1β (p53-independent) splice variants, and the DMP1β/α ratio increases with neoplastic transformation of breast epithelial cells. This process is associated with high DMP1β protein expression and shorter survival of breast cancer (BC) patients. Accumulating pieces of evidence show that ARF is frequently inactivated by aberrant splicing in human cancers, demonstrating its involvement in human malignancies. Splice variants from the MDM2 locus promote cell growth in culture and accelerate tumorigenesis in vivo. Human cancers expressing these splice variants are associated with advanced stage/metastasis, and ...Continue Reading

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Citations

Aug 25, 2016·International Journal of Cancer. Journal International Du Cancer·Elizabeth A FryKazushi Inoue
Apr 14, 2017·Cancer Investigation·Robert D KendigKazushi Inoue
Oct 6, 2017·Genes·Nancy Martínez-MontielRebeca D Martínez-Contreras
Feb 15, 2018·International Journal of Molecular Sciences·Nancy Martinez-MontielRebeca Martinez-Contreras
Mar 22, 2016·Biomarkers in Cancer·Kazushi Inoue, Elizabeth A Fry
Jan 3, 2019·Cancer Investigation·Elizabeth A Fry, Kazushi Inoue
Nov 23, 2018·Cancers·Bi-Dar Wang, Norman H Lee
Nov 7, 2018·Cancer Investigation·Kazushi Inoue, Elizabeth A Fry
Sep 19, 2019·Cells·Pietro CarotenutoAnnapina Russo
Aug 8, 2020·Biomolecules·Jinho SeoJaewhan Song
Oct 31, 2020·International Journal of Molecular Sciences·Elizabeth A FryKazushi Inoue
Sep 28, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Mei GuoJun Dou
Apr 17, 2021·Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology·Emilia MarttilaTuula Salo

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