A role for VICKZ proteins in the progression of colorectal carcinomas: Regulating lamellipodia formation

G. Vainer, E. Vainer-Mossel, A. Pikarsky, Shailesh M. Shenoy, F. Oberman, A. Yeffet, Robert H. Singer, E. Pikarsky, J. K. Yisraeli

Research output: Contribution to journalArticle

32 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)445-456
Number of pages12
JournalJournal of Pathology
Volume215
Issue number4
DOIs
StatePublished - Aug 2008

Fingerprint

Pseudopodia
Colorectal Neoplasms
Proteins
RNA
Neoplasm Metastasis
Cell Movement
Neoplasms
Lymph Nodes
RNA-Binding Proteins
Neural Crest
RNA Stability
Embryonic Development
Disease Progression
Actins
Colon
Staining and Labeling
Lung
Messenger RNA

Keywords

  • Actin cytoskeleton
  • Colorectal carcinoma metastasis
  • Igf2 mRNA binding proteins
  • Immunohistochemistry
  • Intracellular RNA localization
  • Kymographs
  • RNA binding proteins

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Vainer, G., Vainer-Mossel, E., Pikarsky, A., Shenoy, S. M., Oberman, F., Yeffet, A., ... Yisraeli, J. K. (2008). A role for VICKZ proteins in the progression of colorectal carcinomas: Regulating lamellipodia formation. Journal of Pathology, 215(4), 445-456. https://doi.org/10.1002/path.2376

A role for VICKZ proteins in the progression of colorectal carcinomas : Regulating lamellipodia formation. / Vainer, G.; Vainer-Mossel, E.; Pikarsky, A.; Shenoy, Shailesh M.; Oberman, F.; Yeffet, A.; Singer, Robert H.; Pikarsky, E.; Yisraeli, J. K.

In: Journal of Pathology, Vol. 215, No. 4, 08.2008, p. 445-456.

Research output: Contribution to journalArticle

Vainer, G, Vainer-Mossel, E, Pikarsky, A, Shenoy, SM, Oberman, F, Yeffet, A, Singer, RH, Pikarsky, E & Yisraeli, JK 2008, 'A role for VICKZ proteins in the progression of colorectal carcinomas: Regulating lamellipodia formation', Journal of Pathology, vol. 215, no. 4, pp. 445-456. https://doi.org/10.1002/path.2376
Vainer, G. ; Vainer-Mossel, E. ; Pikarsky, A. ; Shenoy, Shailesh M. ; Oberman, F. ; Yeffet, A. ; Singer, Robert H. ; Pikarsky, E. ; Yisraeli, J. K. / A role for VICKZ proteins in the progression of colorectal carcinomas : Regulating lamellipodia formation. In: Journal of Pathology. 2008 ; Vol. 215, No. 4. pp. 445-456.
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