PMID- 22824798
OWN - NLM
STAT- MEDLINE
DCOM- 20130827
LR  - 20130620
IS  - 1476-5594 (Electronic)
IS  - 0950-9232 (Linking)
VI  - 32
IP  - 25
DP  - 2013 Jun 20
TI  - Transducer of Cdc42-dependent actin assembly promotes breast cancer invasion and 
      metastasis.
PG  - 3080-90
LID - 10.1038/onc.2012.317 [doi]
AB  - Metastatic breast adenocarcinomas display activation signatures for signaling 
      pathways that trigger cell motility and tissue invasion. Here, we report that the 
      adaptor protein transducer of Cdc42-dependent actin assembly-1 (Toca-1) is 
      expressed in highly invasive breast cancers and regulates their metastatic 
      phenotypes. We show that Toca-1 localizes to the filamentous actin-rich core of 
      invadopodial protrusions actively degrading the extracellular matrix (ECM). 
      Toca-1 colocalizes with Cortactin, and we show that this interaction is mediated 
      by the SH3 domain of Toca-1. Stable knockdown (KD) of Toca-1 expression in 
      MDA-MB-231 cells led to a significant defect in epidermal growth factor 
      (EGF)-induced cell migration and invasion. Toca-1 KD cells also showed 
      significant defects in EGF- and Src-induced ECM digestion and formation of 
      invadopodial membrane protrusions. To test the role of Toca-1 in metastasis, we 
      achieved stable Toca-1 KD in both human and rat metastatic breast adenocarcinoma 
      cell lines. Orthotopic tumor xenografting of control and Toca-1 KD cells in 
      natural-killer /B-/T-cell-deficient mice revealed a significant defect in 
      spontaneous lung metastases with Toca-1 silencing in vivo. In contrast, no 
      defects in primary tumor growth or lung seeding following tail vein injection of 
      Toca-1 KD cells was observed, suggesting that Toca-1 functions at an early step 
      in the dissemination of metastatic breast tumor cells. Taken together, our 
      results identify Toca-1 as a proinvasive protein in breast adenocarcinoma and a 
      potential therapeutic target to limit tumor metastasis.
FAU - Chander, H
AU  - Chander H
AD  - Cancer Biology & Genetics Division, Queen's Cancer Research Institute, Kingston, 
      Ontario, Canada.
FAU - Truesdell, P
AU  - Truesdell P
FAU - Meens, J
AU  - Meens J
FAU - Craig, A W B
AU  - Craig AW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120723
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Carrier Proteins)
RN  - 0 (Cortactin)
RN  - 0 (FNBP1L protein, human)
RN  - 62229-50-9 (Epidermal Growth Factor)
SB  - IM
MH  - Adenocarcinoma/metabolism/*pathology
MH  - Animals
MH  - Breast Neoplasms/metabolism/*pathology
MH  - Carrier Proteins/genetics/*metabolism
MH  - Cell Line, Tumor
MH  - Cell Movement
MH  - Cell Surface Extensions/metabolism
MH  - Cortactin
MH  - Epidermal Growth Factor/metabolism
MH  - Extracellular Matrix/*metabolism
MH  - Female
MH  - Humans
MH  - Mice
MH  - Neoplasm Invasiveness
MH  - Neoplasm Metastasis
MH  - Rats
EDAT- 2012/07/25 06:00
MHDA- 2013/08/28 06:00
CRDT- 2012/07/25 06:00
PHST- 2012/07/25 06:00 [entrez]
PHST- 2012/07/25 06:00 [pubmed]
PHST- 2013/08/28 06:00 [medline]
AID - onc2012317 [pii]
AID - 10.1038/onc.2012.317 [doi]
PST - ppublish
SO  - Oncogene. 2013 Jun 20;32(25):3080-90. doi: 10.1038/onc.2012.317. Epub 2012 Jul 
      23.