Neural Wiskott-Aldrich syndrome protein(N-WASP)promotes distant metastasis in pancreatic ductal adenocarcinoma via activation of LOXL2

Pancreatic ductal adenocarcinoma(PDAC)is one of the most aggressive solid malignancies.A specific mechanism of its metastasis has not been established.In this study,we investigated whether Neural Wiskott-Aldrich syndrome protein(N-WASP)plays a role in distant metastasis of PDAC.We found that N-WASP is markedly expressed in clinical patients with PDAC.Clinical analysis showed a notably more distant metastatic pattern in the N-WASP-high group compared to the N-WASP-low group.N-WASP was noted to be a novel mediator of epithelialmesenchymal transition(EMT)via gene expression profile studies.Knockdown of N-WASP in pancreatic cancer cells significantly inhibited cell invasion,migration,and EMT.We also observed positive association of lysyl oxidase-like 2(LOXL2)and focal adhesion kinase(FAK)with the N-WASP-mediated response,wherein EMT and invadopodia function were modulated.Both N-WASP and LOXL2 depletion significantly reduced the incidence of liver and lung metastatic lesions in orthotopic mouse models of pancreatic cancer.These results elucidate a novel role for N-WASP signaling associated with LOXL2 in EMT and invadopodia function,with respect to regulation of intercellular communication in tumor cells for promoting pancreatic cancer metastasis.These findings may aid in the development of therapeutic strategies against pancreatic cancer.

Low cross-talk, deep subwavelength plasmonic metal/insulator/metal waveguide intersections with broadband tunability

We suggest a low cross-talk plasmonic cross-connector based on a metal/insulator/metal cavity and waveguides.We separately investigate the isolated cavity mode, the waveguide mode, and the combination of cavity and waveguide modes using a finite-different time-domain method. Due to resonant tunneling and the cutoff frequency of the odd waveguide mode, our proposed structure achieves a high throughput transmission ratio and eliminates cross-talk. Furthermore, the proposed structure has a broadband tunability of 587 nm, which can be achieved by modulating the cavity air gap thickness. This structure enables the miniaturization of photonic integrated circuits and sensing applications.