NHERF1, a novel GPER associated protein, increases stability and activation of GPER in ER-positive breast cancer

G protein-coupled estrogen receptor (GPER) plays an important role in mediating the effects of estradiol. High levels of GPER have been implicated to associate with the malignant progress of invasive breast cancer (IBC). However, the mechanisms by which GPER protein levels were regulated remain unclear. In this study, PDZ protein Na+/H+ exchanger regulatory factor (NHERF1) was found to interact with GPER in breast cancer cells. This interaction was mediated by the PDZ2 domain of NHERF1 and the carboxyl terminal PDZ binding motif of GPER. NHERF1 was demonstrated to facilitate GPER expression at post-transcriptional level and improve GPER protein stability by inhibiting the receptor degradation via ubiquitin-proteasome pathway in a GPER/NHERF1 interaction-dependent manner. In addition, GPER protein levels are positively associated with NHERF1 protein levels in a panel of estrogen receptor (ER)-positive breast cancer cells. Furthermore, analysis of clinical IBC data from The Cancer Genome Atlas (TCGA) showed no significant difference in GPER mRNA levels between ER-positive IBC and normal breast tissues. However, gene set enrichment analysis (GSEA) showed that GPER signaling is ultra-activated in ER-positive IBC when compared with normal and its activation is positively associated with NHERF1 mRNA levels. Taken together, our findings identify NHERF1 as a new binding partner for GPER and its overexpression promotes protein stability and activation of GPER in ER-positive IBC. Our data indicate that regulation of GPER stability by NHERF1 may contribute to GPER-mediated carcinogenesis in ER-positive IBC

EpCAM-Positive Hepatocellular Carcinoma Cells Are Tumor-Initiating Cells With Stem/Progenitor Cell Features

Cancer progression/metastases and embryonic development share many properties including cellular plasticity, dynamic cell motility, and integral interaction with the microenvironment. We hypothesized that the heterogeneous nature of hepatocellular carcinoma (HCC) may be, in part, due to the presence of hepatic cancer cells with stem/progenitor features

Identification of microRNA-181 by genome-wide screening as a critical player in EpCAM-positive hepatic cancer stem cells

MicroRNAs (miRNAs) are endogenous small non-coding RNAs that regulate gene expression with functional links to tumorigenesis. Hepatocellular carcinoma (HCC) is the most common type of liver cancer and it is heterogeneous in clinical outcomes and biological activities. Recently, we have identified a subset of highly invasive EpCAM+ HCC cells from AFP+ tumors with cancer stem/progenitor cell features, i.e., the abilities to self-renew, differentiate and initiate aggressive tumors in vivo. Here, using a global microarray-based microRNA profiling approach followed by validation with quantitative reverse transcription polymerase chain reaction, we have demonstrated that conserved miR-181 family members were upregulated in EpCAM+AFP+ HCCs and in EpCAM+ HCC cells isolated from AFP+ tumors. Moreover, miR-181 family members were highly expressed in embryonic livers and in isolated hepatic stem cells. Importantly, inhibition of miR-181 led to a reduction in EpCAM+ HCC cell quantity and tumor initiating ability, while exogenous miR-181 expression in HCC cells resulted in an enrichment of EpCAM+ HCC cells. We have found that miR-181 could directly target hepatic transcriptional regulators of differentiation (i.e., CDX2 and GATA6) and an inhibitor of wnt/β-catenin signaling (i.e., NLK). Taken together, our results define a novel regulatory link between miR-181s and human EpCAM+ liver cancer stem/progenitor cells and imply that molecular targeting of miR-181 may eradicate HCC

Antioxidant response of the invasive herb Ambrosia artemisiifolia L. to different irradiance levels

The exotic invasive Ambrosia artemisiifolia L. and a native co-occurring species in southern China, Urena lobata L., were compared to investigate the possible protective role of leaf antioxidant systems in the acclimation of invasive plants to different irradiance levels. Antioxidant activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) were examined under four irradiance regimes: 10% (dense shade), 30% (low irradiance), 55% (medium irradiance) and 100% (full irradiance). Free proline (Pro) content and the rate of lipid peroxidation in terms of malondialdehyde (MDA) content, glutathione reductase (GR), and tea polyphenols (TP) were also assessed under the different irradiance regimes. Antioxidant enzyme activity of SOD and CAT and the MDA, GR and TP contents for the two species increased with increasing irradiance levels. Invasive A. artemisiifolia was able to scavenge oxygen radicals more efficiently at higher irradiance levels by enhancing CAT activity and GR and TP contents although leaf SOD activity was not greatly enhanced. This exotic species also maintained normal physiological functions when subjected to low irradiance, which might be attributed to the increase in POD activity with decreasing irradiance levels. The higher efficiency of adaptive responses of antioxidant enzymes may protect plants from irradiance-induced stress and may contribute to the invasiveness of A. artemisiifolia in subtropical and tropical regions.Dans le sud de la Chine, l’espèce exotique envahissante Ambrosia artemisiifolia L. a été comparée à une espèce indigène compagne, Urena lobata L., afin d’évaluer le rôle protecteur potentiel fourni par les systèmes antioxydants de la feuille lors de l’acclimatation des plantes envahissantes soumises à différents taux de flux énergétique. Les activités antioxydants de la superoxyde dismutase (SOD), de la peroxydase (POD) et de la catalase (CAT) ont été examinées sous quatre régimes de flux énergétique : 10 % (ombrage dense), 30 % (faible flux énergétique), 55 % (flux énergétique moyen) et 100 % (flux énergétique complet). Le contenu en proline libre (Pro) et le taux de peroxydation lipidique en termes de malonaldéhyde (MDA), de réductase de glutathion (RG) et de polyphénols de thé (PT) ont également été évalués pour différents taux de flux énergétique. Les activités enzymatiques antioxydantes de SOD et de CAT et les contenus en MDA, RG et PT des deux espèces ont augmenté avec l’augmentation des taux de flux énergétique. L’espèce invasive A. artemisiifolia était en mesure de récupérer les radicaux d’oxygène plus efficacement à un taux de flux énergétique plus élevé grâce à une activité accrue de la CAT et des contenus de RG et PT plus élevés, bien que l’activité de la SOD dans la feuille n’ait pas beaucoup augmentée. Cette espèce exotique a également maintenu des fonctions physiologiques normales lorsque soumise à de faible taux de flux énergétique, ce qui pourrait être attribuable à l’augmentation de l’activité de la POD en lien avec une diminution du taux de flux énergétique. Une plus grande efficacité des réactions adaptatives des enzymes antioxidants pourrait protéger les plantes du stress relié au flux énergétique et contribuer à l’envahissement de l’A. artemisiifolia dans les régions tropicales et subtropicales

Ultralong Organic Room-Temperature Phosphorescence of Electron-donating and Commercially Available Host and Guest Molecules through Efficient Förster Resonance Energy Transfer

Ultralong organic room-temperature phosphorescence (RTP) materials have attracted great attention recently due to its diverse application potentials. Several ultralong organic RTP materials mimicking the host-guest architecture of inorganic systems have been exploited successfully. However, complicated synthesis and high expenditure are still inevitable in these cases. Herein, we develop a series of novel host–guest organic phosphore systems, in which all chromophores are electron-rich, commercially available and halogen atom free. The maximum phosphorescence efficiency and the longest lifetime reach at 23.6% and 362 ms, respectively. Most importantly, experimental results and theoretical calculation indicate that the host molecules not only play a vital role in providing a rigid environment to suppress non-radiative decay of the guest, but also show a synergistic effect to the guest through Förster energy transfer (FERT). The commercial availability, facile preparation and unique properties also make these new host-guest materials an excellent candidate for anti-counterfeiting devices