BackgroundBreast cancer is the most prevalent cancer in women worldwide and metastatic breast cancer has very poor prognosis. Inflammation has been implicated in migration and metastasis of breast cancer, although the exact molecular mechanism remains elusive.Principal FindingsWe show that the pro-inflammatory endotoxin Lipopolysaccharide (LPS) upregulates the expression of Metadherin (MTDH), a recently identified oncogene, in a number of breast cancer lines. Stable knockdown of MTDH by shRNA in human breast MDA-MB-231 cells abolishes LPS-induced cell migration and invasion as determined by several in vitro assays. In addition, knockdown of MTDH diminishes Nuclear Factor-kappa B (NF-κB) activation by LPS and inhibited LPS-induced IL-8 and MMP-9 production.ConclusionsThese results strongly suggest that MTDH is a pivotal molecule in inflammation-mediated tumor metastasis. Since NF-κB, IL-8 and MMP-9 play roles in LPS-induced invasion or metastasis, the mechanism of MTDH-promoted invasion and metastasis may be through the activation of NF-κB, IL-8 and MMP-9, also suggesting a role of MTDH in regulating both inflammatory responses and inflammation-associated tumor invasion. These findings indicate that MTDH is involved in inflammation-induced tumor progression, and support that MTDH targeting therapy may hold promising prospects in treating breast cancer.

The aryne cobalt complex [Co(4-CF 3 -η 2 -C 6 F 3 )(PMe 3 ) 3 ] (1) was formed from the reaction of [Co(PMe 3 ) 4 ] and perfluorinated toluene through selective activation of two C-F bonds of perfluorotoluene. A mechanism for the formation of complex 1 is proposed and in most parts experimentally verified. Following this mechanism, a synergistic effect of an electron-rich cobalt(0) center and one of its trimethylphosphine ligands is responsible for the C-F activation of two carbon-fluorine bonds of perfluorotoluene. The detection of difluorotrimethylphoshphorane as the sole byproduct provides strong evidence for this mechanism. Complex [Co(4-CF 3 -C 6 F 4 )(PMe 3 ) 3 ] (4), an intermediate of the proposed mechanism to the aryne complex, was also isolated and structurally characterized. Complex 4 transforms to complex 1 via activation of a second C-F bond of a perfluorotolyl ligand only in the presence of trimethylphosphine in the reaction mixture. Complex 4 reacts with CO under atmospheric pressure and room temperature to give [Co(4-CF 3 -C 6 F 4 )(CO) 2 (PMe 3 ) 2 ] (6) and with bromobenzene via one-electron oxidative addition of the C-Br bond to give the cobalt(II) bromide [CoBr(4-CF 3 -C 6 F 4 )(PMe 3 ) 3 ] (8) and a C-C-coupling product, 4-phenylheptafluorotoluene (7). The structures of complexes 1, 4, and 8 were determined by X-ray crystallography.

The reactions of unsymmetrical N-heterocyclic carbene (NHC) [CNC]-pincer preligands with CoMe­(PMe3)4 gave rise to NHC [CNC]-pincer cobalt­(III) hydrides, [(CcarbeneNaminoCnaphthyl)­Co­(H)­(PMe3)2] (3a) and (3b), via Csp2–H activation and the unexpected trans-bischelate [Ccarbene, Namino] cobalt­(II) complexes 4a and 4b via a disproportionation reaction, respectively. It was found that both 3a and 3b are efficient catalysts for hydrosilylation of alkenes. With aryl alkenes as substrates, 3a has high Markovnikov selectivity in excellent yields, while 3a is an efficient anti-Markovnikov catalyst in good yields with alkyl alkenes as substrates. The catalytic process could be promoted with pyridine N-oxide as an initiator. The catalytic mechanisms for the two different selectivities were proposed. Complexes 3a, 3b, 4a, and 4b were characterized by spectroscopic methods, and the molecular structures of 3b, 4a, and 4b were determined by single crystal X-ray diffraction.

Reaction of the N-benzylidene-1-naphthylamine with CoMe(PMe 3 ) 4 afforded the hydrido CNC pincer cobalt complex CoH(PMe 3 ) 2 [(C 6 H 4 )CHN(C 10 H 6 )] (1) via double C−H bond activation. In the 1 H NMR spectrum, a triplet at −18.98 ppm is the typical signal of the hydrido ligand (Co−H). Complex 1 reacted with haloalkane (CH 3 I and EtBr) to deliver CoX(PMe 3 ) 2 ((C 6 H 4 )CHN(C 10 H 6 )) (X = I (2); Br (3)). However, the reactions of complex 1 with HCl and trifluoroacetic acid (TFA) delivered HCoCl(PMe 3 ) 2 ((C 6 H 4 )-CHN(C 10 H 7 )) (4) and HCo(OCOCF 3 )(PMe 3 ) 2 ((C 6 H 4 )-CHN(C 10 H 7 )) ( 5) with the cleavage of the Co− C(naphthyl) bond. In the 1 H NMR spectra, the signals of the hydrido ligands were found at −21.31 (4) and −18.71 (5) ppm. A reaction of complex 1 with DCl was carried out to prove that the hydrogen atom eliminated to the naphthyl carbon comes from HCl. Complex 1 reacted with acetylacetone, resulting in the formation of Co(acac)(PMe 3 ) 2 ((C 6 H 5 )CHNH-(C 10 H 6 )) (7). Complex 1 was found to be an efficient catalyst for hydrosilylation of aldehydes and ketones. The molecular structures of complex 1, 2, 4, and 7 were determined by X-ray single-crystal diffraction.

Three novel [CNN]-pincer nickel(ii) complexes with NHC-amine arms were synthesized in three steps. Complex was proven to be an efficient catalyst for the Kumada coupling of aryl chlorides or aryl dichlorides under mild conditions.