MUC4 activates HER2 signalling and enhances the motility of human ovarian cancer cells

The mucin MUC4 is a high molecular weight transmembrane glycoprotein. It consists of a mucin-type subunit (MUC4α) and a transmembrane growth factor-like subunit (MUC4β). The mucin MUC4 is overexpressed in many epithelial malignancies including ovarian cancer, suggesting a possible role in the pathogenesis of these cancers. In this study, we investigated the functional role of MUC4 in the human ovarian cancer cell line SKOV3. The mucin MUC4 was ectopically expressed by stable transfection, and its expression was examined by western blot and confocal microscopy analyses. The in vitro studies demonstrated an enhanced motility of MUC4-expressing SKOV3 cells compared with the vector-transfected cells. The mucin MUC4 expression was associated with apparent changes in actin organisation, leading to the formation of microspike, lammelopodia and filopodia-like cellular projections. An enhanced protein expression and activation of HER2, a receptor tyrosine kinase, was also seen, although no significant change was observed in HER-2 transcript levels in the MUC4-transfected SKOV3 cells. Reciprocal co-immunoprecipitation revealed an interaction of MUC4 with HER2. Further, the MUC4-overexpressing SKOV3 cells exhibited an increase in the phosphorylation of focal adhesion kinase (FAK), Akt and ERK, downstream effectors of HER2. Taken together, our findings demonstrate that MUC4 plays a role in ovarian cancer cell motility, in part, by altering actin arrangement and potentiating HER2 downstream signalling in these cells

Euclid:Identifying the reddest high-redshift galaxies in the Euclid Deep Fields with gradient-boosted trees

Context. ALMA observations show that dusty, distant, massive (M* &amp; 1011 M ) galaxies usually have a remarkable star-formation activity, contributing of the order of 25% of the cosmic star-formation rate density at z 3 5, and up to 30% at z ∼ 7. Nonetheless, they are elusive in classical optical surveys, and current near-IR surveys are able to detect them only in very small sky areas. Since these objects have low space densities, deep and wide surveys are necessary to obtain statistically relevant results about them. Euclid will potentially be capable of delivering the required information, but, given the lack of spectroscopic features at these distances within its bands, it is still unclear if Euclid will be able to identify and characterise these objects. Aims. The goal of this work is to assess the capability of Euclid, together with ancillary optical and near-IR data, to identify these distant, dusty, and massive galaxies based on broadband photometry. Methods. We used a gradient-boosting algorithm to predict both the redshift and spectral type of objects at high z. To perform such an analysis, we made use of simulated photometric observations that mimic the Euclid Deep Survey, derived using the state-of-the-art Spectro-Photometric Realizations of Infrared-selected Targets at all-z (SPRITZ) software. Results. The gradient-boosting algorithm was found to be accurate in predicting both the redshift and spectral type of objects within the simulated Euclid Deep Survey catalogue at z &gt; 2, while drastically decreasing the runtime with respect to spectral-energy-distribution-fitting methods. In particular, we studied the analogue of HIEROs (i.e. sources selected on the basis of a red H - [4:5] &gt; 2:25), combining Euclid and Spitzer data at the depth of the Deep Fields. These sources include the bulk of obscured and massive galaxies in a broad redshift range, 3 &lt; z &lt; 7. We find that the dusty population at 3 . z . 7 is well identified, with a redshift root mean squared error and catastrophic outlier fraction of only 0:55 and 8:5% (HE = 26), respectively. Our findings suggest that with Euclid we will obtain meaningful insights into the impact of massive and dusty galaxies on the cosmic star-formation rate over time.</p

Involvement of focal adhesion kinase in cellular invasion of head and neck squamous cell carcinomas via regulation of MMP-2 expression

Focal adhesion kinase (FAK) is considered intimately involved in cancer progression. Our previous research has demonstrated that overexpression of FAK is an early and frequent event in squamous cell carcinomas of the supraglottic larynx, and it is associated with the presence of metastases in cervical lymph nodes. The purpose of this study was to examine the functional role of FAK in the progression of head and neck squamous cell carcinomas (HNSCC). To this end, expression of FAK-related nonkinase (FRNK) or small interfering RNA (siRNA) against FAK was used to disrupt the FAK-induced signal transduction pathways in the HNSCC-derived SCC40 and SCC38 cell lines. Similar phenotypic effects were observed with the two methodological approaches in both cell lines. Decreased cell attachment, motility and invasion were induced by FRNK and FAK siRNA, whereas cell proliferation was not impaired. In addition, increased cell invasion was observed upon FAK overexpression in SCC cells. FRNK expression resulted in a downregulation of MMP-2 and MMP-9 expression. Interestingly, MMP-2 overexpression in FRNK-expressing cells rescued FRNK inhibition of cell invasion. This is the first demonstration of a direct rescue of impaired cell invasion by the re-expression of MMP-2 in a tumour cell type with decreased expression of functional FAK. Collectively, these data reported here support the conclusion that FAK enhances invasion of HNSCC by promoting both increased cell motility and MMP-2 production, thus providing new insights into possible therapeutic intervention strategies

Carcinoma Matrix Controls Resistance to Cisplatin through Talin Regulation of NF-kB

Extracellular matrix factors within the tumor microenvironment that control resistance to chemotherapeutics are poorly understood. This study focused on understanding matrix adhesion pathways that control the oral carcinoma response to cisplatin. Our studies revealed that adhesion of HN12 and JHU012 oral carcinomas to carcinoma matrix supported tumor cell proliferation in response to treatment with cisplatin. Proliferation in response to 30 µM cisplatin was not observed in HN12 cells adherent to other purified extracellular matrices such as Matrigel, collagen I, fibronectin or laminin I. Integrin β1 was important for adhesion to carcinoma matrix to trigger proliferation after treatment with cisplatin. Disruption of talin expression in HN12 cells adherent to carcinoma matrix increased cisplatin induced proliferation. Pharmacological inhibitors were used to determine signaling events required for talin deficiency to regulate cisplatin induced proliferation. Pharmacological inhibition of NF-kB reduced proliferation of talin-deficient HN12 cells treated with 30 µM cisplatin. Nuclear NF-kB activity was assayed in HN12 cells using a luciferase reporter of NF-kB transcriptional activity. Nuclear NF-kB activity was similar in HN12 cells adherent to carcinoma matrix and collagen I when treated with vehicle DMSO. Following treatment with 30 µM cisplatin, NF-kB activity is maintained in cells adherent to carcinoma matrix whereas NF-kB activity is reduced in collagen I adherent cells. Expression of talin was sufficient to trigger proliferation of HN12 cells adherent to collagen I following treatment with 1 and 30 µM cisplatin. Talin overexpression was sufficient to trigger NF-kB activity following treatment with cisplatin in carcinoma matrix adherent HN12 cells in a process disrupted by FAK siRNA. Thus, adhesions within the carcinoma matrix create a matrix environment in which exposure to cisplatin induces proliferation through the function of integrin β1, talin and FAK pathways that regulate NF-kB nuclear activity

Euclid preparation: XXX. Performance assessment of the NISP red grism through spectroscopic simulations for the wide and deep surveys

This work focusses on the pilot run of a simulation campaign aimed at investigating the spectroscopic capabilities of the Euclid Near-Infrared Spectrometer and Photometer (NISP), in terms of continuum and emission line detection in the context of galaxy evolutionary studies. To this purpose, we constructed, emulated, and analysed the spectra of 4992 star-forming galaxies at 0:3 ≥ z ≥ 2:5 using the NISP pixel-level simulator. We built the spectral library starting from public multi-wavelength galaxy catalogues, with value-added information on spectral energy distribution (SED) fitting results, and stellar population templates from Bruzual & Charlot (2003, MNRAS, 344, 1000). Rest-frame optical and near-IR nebular emission lines were included using empirical and theoretical relations. Dust attenuation was treated using the Calzetti extinction law accounting for the differential attenuation in line-emitting regions with respect to the stellar continuum. The NISP simulator was configured including instrumental and astrophysical sources of noise such as the dark current, read-out noise, zodiacal background, and out-of-field stray light. In this preliminary study, we avoided contamination due to the overlap of the slitless spectra. For this purpose, we located the galaxies on a grid and simulated only the first order spectra.We inferred the 3.5δ NISP red grism spectroscopic detection limit of the continuum measured in the H band for star-forming galaxies with a median disk half-light radius of 0: 004 at magnitude H = 19:5 = 0:2ABmag for the Euclid Wide Survey and at H = 20:8 = 0:6ABmag for the Euclid Deep Survey. We found a very good agreement with the red grism emission line detection limit requirement for the Wide and Deep surveys. We characterised the effect of the galaxy shape on the detection capability of the red grism and highlighted the degradation of the quality of the extracted spectra as the disk size increased. In particular, we found that the extracted emission line signal-to-noise ratio (S/N) drops by 45% when the disk size ranges from 0: 0025 to 100. These trends lead to a correlation between the emission line S/N and the stellar mass of the galaxy and we demonstrate the effect in a stacking analysis unveiling emission lines otherwise too faint to detect

Euclid: Identifying the reddest high-redshift galaxies in the Euclid Deep Fields with gradient-boosted trees

Context. ALMA observations show that dusty, distant, massive (M* &amp; 1011 M ) galaxies usually have a remarkable star-formation activity, contributing of the order of 25% of the cosmic star-formation rate density at z 3 5, and up to 30% at z ∼ 7. Nonetheless, they are elusive in classical optical surveys, and current near-IR surveys are able to detect them only in very small sky areas. Since these objects have low space densities, deep and wide surveys are necessary to obtain statistically relevant results about them. Euclid will potentially be capable of delivering the required information, but, given the lack of spectroscopic features at these distances within its bands, it is still unclear if Euclid will be able to identify and characterise these objects. Aims. The goal of this work is to assess the capability of Euclid, together with ancillary optical and near-IR data, to identify these distant, dusty, and massive galaxies based on broadband photometry. Methods. We used a gradient-boosting algorithm to predict both the redshift and spectral type of objects at high z. To perform such an analysis, we made use of simulated photometric observations that mimic the Euclid Deep Survey, derived using the state-of-the-art Spectro-Photometric Realizations of Infrared-selected Targets at all-z (SPRITZ) software. Results. The gradient-boosting algorithm was found to be accurate in predicting both the redshift and spectral type of objects within the simulated Euclid Deep Survey catalogue at z &gt; 2, while drastically decreasing the runtime with respect to spectral-energy-distribution-fitting methods. In particular, we studied the analogue of HIEROs (i.e. sources selected on the basis of a red H - [4:5] &gt; 2:25), combining Euclid and Spitzer data at the depth of the Deep Fields. These sources include the bulk of obscured and massive galaxies in a broad redshift range, 3 &lt; z &lt; 7. We find that the dusty population at 3 . z . 7 is well identified, with a redshift root mean squared error and catastrophic outlier fraction of only 0:55 and 8:5% (HE = 26), respectively. Our findings suggest that with Euclid we will obtain meaningful insights into the impact of massive and dusty galaxies on the cosmic star-formation rate over time

Euclid. II. The VIS Instrument

This paper presents the specification, design, and development of the Visible Camera (VIS) on the ESA Euclid mission. VIS is a large optical-band imager with a field of view of 0.54 deg^2 sampled at 0.1" with an array of 609 Megapixels and spatial resolution of 0.18". It will be used to survey approximately 14,000 deg^2 of extragalactic sky to measure the distortion of galaxies in the redshift range z=0.1-1.5 resulting from weak gravitational lensing, one of the two principal cosmology probes of Euclid. With photometric redshifts, the distribution of dark matter can be mapped in three dimensions, and, from how this has changed with look-back time, the nature of dark energy and theories of gravity can be constrained. The entire VIS focal plane will be transmitted to provide the largest images of the Universe from space to date, reaching m_AB>24.5 with S/N >10 in a single broad I_E~(r+i+z) band over a six year survey. The particularly challenging aspects of the instrument are the control and calibration of observational biases, which lead to stringent performance requirements and calibration regimes. With its combination of spatial resolution, calibration knowledge, depth, and area covering most of the extra-Galactic sky, VIS will also provide a legacy data set for many other fields. This paper discusses the rationale behind the VIS concept and describes the instrument design and development before reporting the pre-launch performance derived from ground calibrations and brief results from the in-orbit commissioning. VIS should reach fainter than m_AB=25 with S/N>10 for galaxies of full-width half-maximum of 0.3" in a 1.3" diameter aperture over the Wide Survey, and m_AB>26.4 for a Deep Survey that will cover more than 50 deg^2. The paper also describes how VIS works with the other Euclid components of survey, telescope, and science data processing to extract the cosmological information.Comment: Paper submitted as part of the A&A special issue `Euclid on Sky', which contains Euclid key reference papers and first results from the Euclid Early Release Observation

Euclid Preparation TBD. Characterization of convolutional neural networks for the identification of galaxy-galaxy strong lensing events

Forthcoming imaging surveys will potentially increase the number of known galaxy-scale strong lenses by several orders of magnitude. For this to happen, images of tens of millions of galaxies will have to be inspected to identify potential candidates. In this context, deep learning techniques are particularly suitable for the finding patterns in large data sets, and convolutional neural networks (CNNs) in particular can efficiently process large volumes of images. We assess and compare the performance of three network architectures in the classification of strong lensing systems on the basis of their morphological characteristics. We train and test our models on different subsamples of a data set of forty thousand mock images, having characteristics similar to those expected in the wide survey planned with the ESA mission \Euclid, gradually including larger fractions of faint lenses. We also evaluate the importance of adding information about the colour difference between the lens and source galaxies by repeating the same training on single-band and multi-band images. Our models find samples of clear lenses with $\gtrsim 90\%$ precision and completeness, without significant differences in the performance of the three architectures. Nevertheless, when including lenses with fainter arcs in the training set, the three models' performance deteriorates with accuracy values of $\sim 0.87$ to $\sim 0.75$ depending on the model. Our analysis confirms the potential of the application of CNNs to the identification of galaxy-scale strong lenses. We suggest that specific training with separate classes of lenses might be needed for detecting the faint lenses since the addition of the colour information does not yield a significant improvement in the current analysis, with the accuracy ranging from $\sim 0.89$ to $\sim 0.78$ for the different models

Euclid preparation: LVIII. Detecting extragalactic globular clusters in the Euclid survey

\ua9 The Authors 2025.Extragalactic globular clusters (EGCs) are an abundant and powerful tracer of galaxy dynamics and formation, and their own formation and evolution is also a matter of extensive debate. The compact nature of globular clusters means that they are hard to spatially resolve and thus study outside the Local Group. In this work we have examined how well EGCs will be detectable in images from the Euclid telescope, using both simulated pre-launch images and the first early-release observations of the Fornax galaxy cluster. The Euclid Wide Survey will provide high-spatial resolution VIS imaging in the broad IE band as well as near-infrared photometry (YE, JE, and HE). We estimate that the 24 719 known galaxies within 100 Mpc in the footprint of the Euclid survey host around 830 000 EGCs of which about 350 000 are within the survey\u27s detection limits. For about half of these EGCs, three infrared colours will be available as well. For any galaxy within 50 Mpc the brighter half of its GC luminosity function will be detectable by the Euclid Wide Survey. The detectability of EGCs is mainly driven by the residual surface brightness of their host galaxy. We find that an automated machine-learning EGC-classification method based on real Euclid data of the Fornax galaxy cluster provides an efficient method to generate high purity and high completeness GC candidate catalogues. We confirm that EGCs are spatially resolved compared to pure point sources in VIS images of Fornax. Our analysis of both simulated and first on-sky data show that Euclid will increase the number of GCs accessible with high-resolution imaging substantially compared to previous surveys, and will permit the study of GCs in the outskirts of their hosts. Euclid is unique in enabling systematic studies of EGCs in a spatially unbiased and homogeneous manner and is primed to improve our understanding of many understudied aspects of GC astrophysics