A role for VICKZ proteins in the progression of colorectal carcinomas: regulating lamellipodia formation
- 4 July 2008
- journal article
- research article
- Published by Wiley in The Journal of Pathology
- Vol. 215 (4), 445-456
- https://doi.org/10.1002/path.2376
Abstract
VICKZ proteins are a highly conserved family of RNA binding proteins, implicated in RNA regulatory processes such as intracellular RNA localization, RNA stability, and translational control. During embryogenesis, VICKZ proteins are required for neural crest migration and in adults, the proteins are overexpressed primarily in different cancers. We hypothesized that VICKZ proteins may play a role in cancer cell migration. In patients, VICKZ expression varies with tumour type, with over 60% of colon, lung, and ovarian tumours showing strong expression. In colorectal carcinomas (CRCs), expression is detected at early stages, and the frequency and intensity of staining increase with progression of the disease to lymph node metastases, of which 97% express the protein at high levels. Indeed, in stage II CRC, the level of VICKZ expression in the primary lesion correlates with the degree of lymph node metastasis. In culture, VICKZ proteins rapidly accumulate in processes at the leading edge of PMA‐stimulated SW480 CRC cells, where they co‐localize with β‐actin mRNA. Two distinct cocktails of shRNAs, each targeting all three VICKZ paralogues, cause a dramatic drop in lamellipodia and ruffle formation in stimulated cells. Thus, VICKZ proteins help to facilitate the dynamic cell surface morphology required for cell motility. We propose that these proteins play an important role in CRC metastasis by shuttling requisite RNAs to the lamellipodia of migrating cells. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.Keywords
This publication has 52 references indexed in Scilit:
- VICKZ proteins mediate cell migration via their RNA binding activityRNA, 2007
- Molecular Composition of IMP1 Ribonucleoprotein GranulesMolecular & Cellular Proteomics, 2007
- ZBP1 regulates mRNA stability during cellular stressThe Journal of cell biology, 2006
- Asymmetrical β-actin mRNA translation in growth cones mediates attractive turning to netrin-1Nature Neuroscience, 2006
- Filopodia Formation in the Absence of Functional WAVE- and Arp2/3-ComplexesMolecular Biology of the Cell, 2006
- Localization of all seven messenger RNAs for the actin-polymerization nucleator Arp2/3 complex in the protrusions of fibroblastsJournal of Cell Science, 2005
- Real-Time Visualization of ZBP1 Association with β-Actin mRNA during Transcription and LocalizationCurrent Biology, 2003
- 8q24 Copy number gains and expression of the c‐myc mRNA stabilizing protein CRD‐BP in primary breast carcinomasInternational Journal of Cancer, 2003
- Overexpression of an mRNA-binding protein in human colorectal cancerOncogene, 2001
- Serum-induced signal transduction determines the peripheral location of beta-actin mRNA within the cell.The Journal of cell biology, 1994