INVESTIGADORES
VENTURA Alejandra Cristina
congresos y reuniones científicas
Título:
SHORT-TERM DYNAMICS OF RHOC GTP-ASE IN AGGRESSIVE PHENOTYPES OF BREAST CANCER
Autor/es:
ALEJANDRA C VENTURA; JACQUES-A. SEPULCHRE; ZHIFEN WU; MEI WU; JORGE R TREDICCE; SOFIA D MERAJVER
Lugar:
Ann Arbor, Michigan
Reunión:
Simposio; CANCER RESEARCH SYMPOSIUM; 2008
Institución organizadora:
University of Michigan Comprehensive Cancer Center
Resumen:
The most damaging change
during cancer progression is the growth of metastases. The protein RhoC GTPase
was found to be crucial in that process in different cancers, particularly, in
a highly aggressive form of breast cancer, termed inflammatory breast cancer
(IBC). RhoC is a molecular switch cycling between inactive (GDP-bound) and
active (GTP-bound) states, tightly regulated by several regulatory proteins. We
have developed a dual mathematical-experimental approach to understand this
cycle and its deregulation in breast cancer cells in comparison with normal
ones. A major impact of this work is to quantitatively predict the effects of
drugs targeted against RhoC in cancer.
We have found that the activation profile of
RhoC after stimulation with lysophophatidic acid (LPA) is similar to those of
other small GTPases. Unexpectedly however, a significant and rapid increase in
RhoC protein abundance accompanies this activation profile. We have found that
this increase is due to a previously unrecognized feedback loop between the
activation cycle and the protein synthesis-degradation balance. We have studied
this atypical behavior in detail. The correlation of this novel finding with
the aggressiveness of IBC cells is unveiled, as well as its impact in drug
strategies.