Transcript
March 9-12, 2011, Orlando, Florida
Cell invasion programs in metastatic cancer
Martin H. Hager, Ph.D., Instructor in Surgery Children’s Hospital Boston
Harvard Medical School
Dr. Martin H. Hager, Instructor in Surgery
Harvard Medical School
The metastatic cascade
Tumor cell invasion mechanisms
MAT
EMT
Mesenchymal cell movement
Tumor cell invasion mechanisms
MAT
EMT
Amoeboid cell movement
Identification of significant focal copy number alterations
Beroukhim et al. Nat. 463, 18 Feb 2010
DIAPH3 loss is associated with metastatic prostate cancer
Breast Carcinoma
Prostate Carcinoma
Hepatocellular Carcinoma Chr13
DIAPH3 loss is associated with metastatic prostate cancer
DIA
PH
3 lo
g2
cop
y n
um
ber
un
its
-0.5
0.1
0
-0.1
-0.2
-0.3
-0.4 n=181 n=37
Primary Site
Met
DIA
PH
3 lo
g2
cop
y n
um
ber
un
its
-0.5
0.2
0.1
0
-0.1
-0.2
-0.3
-0.4
Gleason Score
6 8 7 9
n=53 n=12 n=102 n=12 n=36
Met
DIAPH3 loss is associated with metastatic prostate cancer
An unidentified region of HD matches the DIAPH3 gene locus
An unidentified region of HD matches the DIAPH3 gene locus
DRF3 forms a complex with EGFR
DRF3 regulates EGFR trafficking
DRF3 regulates EGFR signaling
DRF3 regulates proliferation and epithelial morphogenesis
Loss of DRF3 cooperates with RAS to promote cell invasion
Loss of DRF3 cooperates with RAS to promote cell invasion
HMEC HRASV12 Control shRNA HMEC HRASV12 DRF3 shRNA
Loss of DRF3 cooperates with RAS to promote cell invasion
Loss of DRF3 promotes an amoeboid phenotype
Loss of DRF3 promotes invasion and metastasis
Supported by:
In collaboration with:
Michael J. Eck, M.D., Ph.D.
David S. Pellman, M.D.
James E. Bradner, M.D.
Richard O. Hynes, Ph.D.
Henry H. Higgs, Ph.D.
Joan S. Brugge, Ph.D.
Jose M. Silva, Ph.D.
William C. Hahn, M.D., Ph.D.
Sizhen Gao, M.D.
Ghassan Mouneimne, Ph.D.
Robert A. Weinberg, Ph.D.
Gregory Hannon, Ph.D.
Ilona N. Holcomb, Ph.D.
William B. Isaacs, Ph.D.
Wennuan Liu, Ph.D.
Acknowledgements:
Michael R. Freeman, Ph.D.
the Freeman lab
Please see poster P24-39 tomorrow, 4:00-5:30 PM (P24 - Genetics and Molecular Biology II)
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