PMID- 18931703
OWN - NLM
STAT- MEDLINE
DCOM- 20090210
LR  - 20181113
IS  - 1476-5594 (Electronic)
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 28
IP  - 3
DP  - 2009 Jan 22
TI  - Aggressiveness of HNSCC tumors depends on expression levels of cortactin, a gene 
      in the 11q13 amplicon.
PG  - 431-44
LID - 10.1038/onc.2008.389 [doi]
AB  - 11q13 amplification is a late-stage event in several cancers that is often 
      associated with poor prognosis. Among 11q13-amplified genes, the actin assembly 
      protein cortactin/CTTN is considered a likely candidate for direct involvement in 
      tumor progression because of its cell motility-enhancing functions. We modulated 
      cortactin expression in head and neck squamous cell carcinoma (HNSCC) cell lines. 
      Cortactin expression levels directly correlated with tumor size, vascularization 
      and cell proliferation in an orthotopic HNSCC in vivo model. In contrast, under 
      normal in vitro culture conditions, cortactin expression levels had no effect on 
      cell proliferation. However, cell lines in which cortactin expression was reduced 
      by knockdown (KD) grew poorly in vitro under harsh conditions of growth factor 
      deprivation, anchorage independence and space constraint. In contrast, 
      overexpression of cortactin enhanced in vitro growth under the same harsh 
      conditions. Surprisingly, defects in growth factor-independent proliferation of 
      cortactin-KD cells were rescued by coculture with cortactin-expressing cells. As 
      the cocultured cells are separated by permeable filters, cortactin-expressing 
      cells must secrete growth-supporting autocrine factors to rescue the cortactin-KD 
      cells. Overall, cortactin expression modulates multiple cellular traits that may 
      allow survival in a tumor environment, suggesting that the frequent 
      overexpression of cortactin in tumors is not an epiphenomenon but rather promotes 
      tumor aggressiveness.
FAU - Clark, E S
AU  - Clark ES
AD  - Department of Cancer Biology, Vanderbilt University, Nashville, TN 37232-6840, 
      USA.
FAU - Brown, B
AU  - Brown B
FAU - Whigham, A S
AU  - Whigham AS
FAU - Kochaishvili, A
AU  - Kochaishvili A
FAU - Yarbrough, W G
AU  - Yarbrough WG
FAU - Weaver, A M
AU  - Weaver AM
LA  - eng
GR  - 1R21 DE018244/DE/NIDCR NIH HHS/United States
GR  - R21 DE018244/DE/NIDCR NIH HHS/United States
GR  - R01 GM075126-02/GM/NIGMS NIH HHS/United States
GR  - R01 GM075126/GM/NIGMS NIH HHS/United States
GR  - R21 DE018244-02/DE/NIDCR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20081020
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Cortactin)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (RNA, Small Interfering)
SB  - IM
MH  - Animals
MH  - Apoptosis/physiology
MH  - Autocrine Communication
MH  - Carcinoma, Squamous Cell/genetics/*pathology
MH  - Cell Proliferation
MH  - Chromosomes, Human, Pair 11/*genetics
MH  - Coculture Techniques
MH  - Cortactin/*genetics
MH  - Gene Expression Regulation, Neoplastic/*physiology
MH  - Head and Neck Neoplasms/genetics/*pathology
MH  - Humans
MH  - Mice
MH  - Mice, Nude
MH  - Neoplasm Invasiveness
MH  - Nerve Growth Factors
MH  - RNA, Small Interfering/pharmacology
MH  - Rats
MH  - Trachea/cytology/transplantation
MH  - Tumor Cells, Cultured
PMC - PMC2709457
MID - NIHMS119375
EDAT- 2008/10/22 09:00
MHDA- 2009/02/12 09:00
PMCR- 2009/07/22
CRDT- 2008/10/22 09:00
PHST- 2008/10/22 09:00 [pubmed]
PHST- 2009/02/12 09:00 [medline]
PHST- 2008/10/22 09:00 [entrez]
PHST- 2009/07/22 00:00 [pmc-release]
AID - onc2008389 [pii]
AID - 10.1038/onc.2008.389 [doi]
PST - ppublish
SO  - Oncogene. 2009 Jan 22;28(3):431-44. doi: 10.1038/onc.2008.389. Epub 2008 Oct 20.