Aggressive forms of cancer are often defined by recurrent chromosomal alterations, yet in most cases, the causal or contributing genetic components remain poorly understood. Here, we utilized microarray informatics to identify candidate oncogenes potentially contributing to aggressive breast cancer behavior. We identified the Rab-coupling protein RCP (also known as RAB11FIP1), which is located at a chromosomal region frequently amplified in breast cancer (8p11-12) as a potential candidate. Overexpression of RCP in MCF10A normal human mammary epithelial cells resulted in acquisition of tumorigenic properties such as loss of contact inhibition, growth-factor independence, and anchorage-independent growth. Conversely, knockdown of RCP in human breast cancer cell lines inhibited colony formation, invasion, and migration in vitro and markedly reduced tumor formation and metastasis in mouse xenograft models. Overexpression of RCP enhanced ERK phosphorylation and increased Ras activation in vitro. As these results indicate that RCP is a multifunctional gene frequently amplified in breast cancer that encodes a protein with Ras-activating function, we suggest it has potential importance as a therapeutic target. Furthermore, these studies provide new insight into the emerging role of the Rab family of small G proteins and their interacting partners in carcinogenesis.
Adsorption
and dissociation processes of gas molecules on bulk
materials and nanomaterials are essential for catalytic conversion
of carbon dioxide (CO2). In this work, we systematically
investigated the CO2 adsorption and dissociation on low
index surfaces of different transition metals by Density Functional
Theory (DFT) calculations. A comparison study demonstrates that the
open surfaces (Fe(100), Ni(100), Ni(110), Rh(100), and Ir(100)) have
stronger interactions with CO2 molecules than the close-packed
surfaces. The order of energy barriers for CO2 dissociation
is Fe(110), Ir(100) < Ru(0001), Rh(100), Co(0001), Ni(100) <
Os(0001), Ni(111) < Ir(111), Rh(111), Ni(110) < Fe(100), Pt(111)
< Cu(100), Pd(111) < Cu(111). The interaction order between
the dissociative CO*, O* species and the surfaces is Fe(100) >
Fe(110)
> Ru(0001) > Os(0001) > Ir(100), Rh(100) > Ni(110) >
Co(0001) > Rh(111),
Ir(111) > Ni(100), Ni(111) > Cu(100) > Pt(111) > Cu(111),
Pd(111).
In addition, we found that the change trend of adsorption energy is
consistent with that of charge transfer amounts from the low index
surfaces to CO2. The Brønsted–Evans–Polanyi
relation showed that the electronic effects of Ni(111) and Ni(110),
Cu(111) and Cu(100) and the geometric effects of Fe(110) and Fe(100),
Ir(111) and Ir(100) have great influence on the CO2 dissociation,
which is closely related to cleavage of C–O in transition states.
Our results may provide an insight into the design of highly efficient
nanocatalysts for CO2-involved reactions.
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