Metastasis is the leading cause of mortality for human non-small cell lung cancer (NSCLC). However, it is difficult to target tumor metastasis because the molecular mechanisms underlying NSCLC invasion and migration remain unclear. Methods: GEO data analyses and IHC analyses were performed to identify that the expression level of AKR1C1, a member of human aldo-keto reductase family, was highly elevated in patients with metastasis or metastatic foci of NSCLC patients. Functional analyses (in vitro and in vivo) and quantitative genomic analyses were preformed to confirm the pro-metastatic effects of AKR1C1 and the underlying mechanisms. The correlation of AKR1C1 with the prognosis of NSCLC patients was evaluated using Kaplan-Meier analyses. Results: in NSCLC patients, AKR1C1 expression was closely correlated with the metastatic potential of tumors. AKR1C1 overexpression in nonmetastatic cancer cells significantly promoted metastasis both in vitro and in vivo, whereas depletion of AKR1C1 in highly metastatic tumors potently alleviated these effects. Quantitative genomic and functional analyses revealed that AKR1C1 directly interacted with STAT3 and facilitated its phosphorylation—thus reinforcing the binding of STAT3 to the promoter regions of target genes—and then transactivated these genes, which ultimately promoted tumor metastasis. Further studies showed that AKR1C1 might facilitate the interaction of STAT3 with its upstream kinase JAK2. Intriguingly, AKR1C1 exerted these pro-metastatic effects in a catalytic-independent manner. In addition, a significant correlation between AKR1C1 and STAT3 pathway was observed in the metastatic foci of NSCLC patients, and the AKR1C1-STAT3 levels were highly correlated with a poor prognosis in NSCLC patients. Conclusions: taken together, we show that AKR1C1 is a potent inducer of NSCLC metastasis. Our study uncovers the active function of AKR1C1 as a key component of the STAT3 pathway, which promotes lung cancer metastasis, and highlights a candidate therapeutic target to potentially improve the survival of NSCLC patients with metastatic disease.

The cyclotron resonance of a two-dimensional electron gas in an InAs quantum well sandwiched between two GaSb layers has been investigated experimentally for its dependence on the magnetic field. Bath the amplitude and the half-width of the resonance show a strong oscillatory behavior, exhibiting a maximum amplitude and correspondingly a minimum half-width when the highest occupied Landau level is half filled. Oscillations for more than ten periods have been observed.From our experiments we can deduce that there is a considerable overlap of the Landau levels, which strongly increases with decreasing magnetic field.The cyclotron resonance (CR) in a two-dimensional electron gas (2DEG) has been investigated extensively for different systems, e.g. , Si metal-oxide-semiconductor structures, ' InSb metal-insulator-semiconductor structures, 2 GaAs heterostructures, 3 and InAs quantum wells.The dependence of the mass, amplitude, and linewidth of the CR on the magnetic field 8 shows a complex behavior. It differs for different systems and sample configurations due to different scattering and interaction mechanisms that are important for the particular situation (e.g. , Refs. 6-9). For some Al"Ga~"As-GaAs heterostructure samples, in particular of not too high electron density Nq, an oscillation of the half-width related to an odd and an even filling factor v Ngh/e8 has been ob-served3' which has been explained by an oscillatory behavior of the screening properties for a 2DEG in a strong magnetic field 8. 3"'2We have investigated CR in a 2DEG of an InAs quantum well'3 sandwiched between two GaSb layers. This system has the advantage of a relatively low effective CR mass m, with corresponding high cyclotron frequencies to, e8/m, . This allows us to study CR down to low magnetic fields and high filling factors. Also of importance is that the charge density Ns and mobility are such that the effect of the optical signal saturation (see below) does not smear out oscillations and the internal CR scattering r, can be determined.Since we can observe a large number of oscillation periods we are able to make detailed statements about the 8 dependence for the situations of both fully filled and half-filled highest Landau levels. In particular,~e can conclude from our measurements that there is a significant overlap of the density of states between the different Landau levels, as has been discussed from magnetic susceptibility, specific™heat, and magnetocapacitance measurements.The experiments~ere performed on molecular-beam-epitaxially grown samples, similar to those described in Refs. 4 and 13. On a GaAs substrate, a buffer layer of GaAs and then a thick layer of GaSb were first grown. This was followed by the InAs well of 20 nm and completed with a GaSb cap of 20 nm. All layers are nominally undoped. This system represents a type-II heterostructure with the GaSb valence band about 150 meV above the InAs conduction band. In this system electrons are transferred from the GaSb into the InAs quantum well, creating, in an ideal case, an ...

Pronounced many-body exciton effects have been observed through photoluminescence in modulation-doped n-type GaAs quantum wells where a near-resonance coincidence exists between a transition involving two-dimensional electrons at the Fermi level in the first conduction subband and an exciton transition from the second conduction subband. Under these conditions, strong and distinct Fermi-edge singularities can be observed near k=0. A magnetic field induces further enhancement of the effect, but also leads to very large, 8 -periodic amplitude variations in the photoluminescence, with excursions over 3 orders of magnitude.There has been a surge of interest in the study of a two-dimensional (2D) electron gas in quantizing magnetic fields by optical methods, motivated in part by attempts to develop spectroscopic probes of the quantum Hall effect ' For example, we have reported recently on results in (In, Ga)As single quantum wells (SQW) where the connection to the integer QHE was argued to have been realized for a particular sample design in terms of optimizing its optical properties as a probe of the 2D electron gas. This design calls for a one-sided modulation-doped quantum well where the Fermi level (EF) lies very near a particular unoccupied conduction subband (typically n, =2). Under such circumstances, the dominant features in the recombination spectrum for such a nearly degenerate circumstance can show pronounced many-body exciton effects, which are closely related to the "Fermi-edge singularities" (ES) observed through photoluminescence or absorption in modulation-doped quantum wells (MDQW), albeit now under specific conditions.In terms of an optical probe, apart from the near energetic degeneracy between the second conduction subband (n, =2) and EF, the details of the heterostructure design also include careful consideration of the electron-hole (eh) wave-function overlap. 'In the asymmetric heterostructures considered here, this overlap can, in principle, be adjusted over a large range by constraining the carriers to opposite sides of the SQW. Hence, the e hCoulomb-(excitonic) energy is also "tunable. "The principal aim of this paper is to show how, within a relatively narrow range in the electron-sheet density (n, ) and the e-h separation, pronounced many-body contributions to interband excitonlike transitions are present in ntype GaAs MDQW's, as viewed through photoluminescence (PL). The application of magnetic fields produces striking effects for hybridized "magnetoexciton" resonances both in terms of amplitude and spectra. Our data suggest that the ES effects are, if anything, enhanced in magnetic fields in ways which suggest their use as an optical probe of the 2D electron gas. At the same time, the experiments also raise questions about the photoholes in terms of their perturbation of the 2D system. This is, needless to say, a critical issue in optical studies of collective 2D electron phenomena such as the fractional QHE and the Wigner crystallization. Figure 1 shows a portion of the photoluminescen...