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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 tumor type, with over 60% of colon, lung, and ovarian tumors showing
strong expression. In colorectal carcinomas (CRC), expression is detected at
early stages, and 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 paralogs, cause a dramatic drop in lamellipodia and ruffle formation in stimulated cells. Thus, VICKZ proteins help 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. |
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