A role for VICKZ proteins in the progression of colorectal carcinomas: regulating lamellipodia formation.
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 beta-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.
Department of Anatomy and Cell Biology, Institute for Medical Research, Hebrew University, POB 12272, Jerusalem, Israel.
G
G
Vainer
E
E
Vainer-Mosse
A
A
Pikarsky
S M
SM
Shenoy
F
F
Oberman
A
A
Yeffet
R H
RH
Singer
E
E
Pikarsky
J K
JK
Yisraeli
D000230:Adenocarcinoma / Q000473:pathology*; D000328:Adult; D002465:Cell Movement; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D018450:Disease Progression; D020868:Gene Silencing; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization / Q000379:methods; D008207:Lymphatic Metastasis; D009361:Neoplasm Invasiveness; D011554:Pseudopodia / Q000737:chemistry / Q000648:ultrastructure; D012333:RNA, Messenger / Q000032:analysis; D034741:RNA, Small Interfering / Q000494:pharmacology; D016601:RNA-Binding Proteins
D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; C485731:ZBP1 protein, human