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Modeling the Transitions between Collective and Solitary Migration Phenotypes in
Cancer Metastasis
#MMPMID26627083
Huang B
; Jolly MK
; Lu M
; Tsarfaty I
; Ben-Jacob E
; Onuchic JN
Sci Rep
2015[Dec]; 5
(?): 17379
PMID26627083
show ga
Cellular plasticity during cancer metastasis is a major clinical challenge. Two
key cellular plasticity mechanisms -Epithelial-to-Mesenchymal Transition (EMT)
and Mesenchymal-to-Amoeboid Transition (MAT) - have been carefully investigated
individually, yet a comprehensive understanding of their interconnections remains
elusive. Previously, we have modeled the dynamics of the core regulatory circuits
for both EMT (miR-200/ZEB/miR-34/SNAIL) and MAT (Rac1/RhoA). We now extend our
previous work to study the coupling between these two core circuits by
considering the two microRNAs (miR-200 and miR-34) as external signals to the
core MAT circuit. We show that this coupled circuit enables four different stable
steady states (phenotypes) that correspond to hybrid epithelial/mesenchymal
(E/M), mesenchymal (M), amoeboid (A) and hybrid amoeboid/mesenchymal (A/M)
phenotypes. Our model recapitulates the metastasis-suppressing role of the
microRNAs even in the presence of EMT-inducing signals like Hepatocyte Growth
Factor (HGF). It also enables mapping the microRNA levels to the transitions
among various cell migration phenotypes. Finally, it offers a mechanistic
understanding for the observed phenotypic transitions among different cell
migration phenotypes, specifically the Collective-to-Amoeboid Transition (CAT).
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