Is it all due to peers? The influence of peers on children's snack purchase decisions.

The objective of this study is to examine whether the presence of peers has an impact on children's snack purchasing decisions. In particular, the research analyzes whether the company of a classmate or friend influences children's brand awareness and price perception, and how these factors affect their snack purchases. An incentive-based discrete choice experiment was conducted with snacks varying in price, brand, and healthiness, using the presence or absence of peers as a between-subject treatment. The data was analyzed using mixed logit models and a multinomial logit model. A total of 128 primary school children aged 8 to 10 years were included in the final data analysis. The findings show that the presence of peers strongly influences children's snack purchase decisions, particularly with respect to product type and price. The results highlight that children tend to conform to the group's decision, highlighting that social influence plays a crucial role in shaping children's decision-making processes. This study is the first to investigate the influence of peers on children's actual purchase decisions, thereby extending previous knowledge of the impact of peers on primary school children to the market domain.

Every step you take: Nudging animal welfare product purchases in a virtual supermarket.

Animal welfare (AW) is a growing concern for consumers in Germany; however, not all consumers regularly purchase products that have been produced according to high AW standards. The goal of the present study is to test the effect of a multilayered nudge to increase the availability and improve the visibility of AW products in a 3D online virtual supermarket (VS). The nudge included a shelf with AW products (referred to as AW shelf) which was made visible through banners and footsteps on the floor of the VS. The sample of this pre-registered experiment consisted of n = 374 German consumers who regularly purchase meat, milk, and eggs. The results demonstrated that the multilayered nudge was highly effective: the percentage of AW products purchased in the nudging condition was almost twice as high as in the control group. Furthermore, we investigated variables that mediate (ease of finding AW products in the VS) and moderate (price sensitivity) the effectiveness of the multilayered nudge, but no evidence for an effect was obtained. We conclude that multilayered nudges may be a promising tool to increase consumers' AW product purchases. More research is needed to replicate this finding with a field study in a real supermarket.

Behavioral factors driving farmers' intentions to adopt spot spraying for sustainable weed control.

Smart Farming Technologies enable plant-specific agrochemical applications which can increase the efficiency and reduce the environmental impacts of agriculture. However, the uptake of Smart Farming Technologies remains slow despite their potential to enhance sustainable transformation of food systems. The design of policies to promote sustainable agricultural technologies requires a holistic understanding of the complex set of factors driving the adoption of innovations at farm level. This study has a focus on behavioral factors, such as pro-environmental attitude, personal innovativeness and moral norms. Based on an online study conducted in Germany, structural equation modelling is applied to test the predictions of an extended version of the Theory of Planned Behavior, using spot spraying, a smart weeding technology, as an example. The results confirm theoretical predictions and show that indicators of attitude, subjective norms, and perceived behavioral control have relevant effects on farmers' adoption intentions. The extended model revealed a medium-sized (small) direct effect of moral norms on the attitude towards spot spraying (adoption intention). Personal innovativeness had a small effect on adoption intention, whereas pro-environmental attitude did not exhibit a clear direction of impact. Methodological and policy implications derived from the results are discussed noting that the inclusion of indicators for moral norms can improve the predictive power of models used in future research in this field. Overall, initiatives aimed at facilitating the exchange of opinions and related moral norms as well as collaboration among peers may contribute to voluntary sustainable innovation as it enhances adoption intentions among farmers.

Fifty shades of grain - Increasing whole grain consumption through daily messages.

Despite numerous health benefits, the majority of consumers, in particular young adults, show low levels of whole grain consumption behaviour (WGCB). In order to increase WGCB, this pre-registered experimental study investigates the effect of a two weeks message intervention. Participants (n = 329) received either information about health benefits, recipe suggestions, a combination of both, or about a control topic. We evaluated WGCB at three time points: prior to, immediately after (post), and one month after the intervention (follow-up). Our findings show that participants read the message on most of the days and on average, evaluate the health-only message most positively. Furthermore, we found that health messages, but not recipe suggestions significantly increase WGCB at the follow-up measure. This effect was serially mediated by attitudes and behavioural intentions at the post-intervention measure, with more positive attitudes and higher intentions leading to more WGCB. Although health messages are an effective tool to influence WGCB, the effect is small in magnitude and consumption levels remain rather low. We discuss implications for future research and for the communication of whole grain related health benefits among different stakeholders in the health sector.

CD44 Contributes to the Regulation of MDR1 Protein and Doxorubicin Chemoresistance in Osteosarcoma.

Osteosarcoma is the most common type of pediatric bone tumor. Despite great advances in chemotherapy during the past decades, the survival rates of osteosarcoma patients remain unsatisfactory. Drug resistance is one of the main reasons, leading to treatment failure and poor prognosis. Previous reports correlated expression of cluster of differentiation 44 (CD44) with drug resistance and poor survival of osteosarcoma patients, however the underlying mechanisms are poorly defined. Here, we investigated the role of CD44 in the regulation of drug chemoresistance, using osteosarcoma cells isolated from mice carrying a mutation of the tumor suppressor neurofibromatosis type 2 (Nf2) gene. CD44 expression was knocked-down in the cells using CRISPR/Cas9 approach. Subsequently, CD44 isoforms and mutants were re-introduced to investigate CD44-dependent processes. Sensitivity to doxorubicin was analyzed in the osteosarcoma cells with modified CD44 expression by immunoblot, colony formation- and WST-1 assay. To dissect the molecular alterations induced by deletion of Cd44, RNA sequencing was performed on Cd44-positive and Cd44-negative primary osteosarcoma tissues isolated from Nf2-mutant mice. Subsequently, expression of candidate genes was evaluated by quantitative reverse transcription PCR (qRT-PCR). Our results indicate that CD44 increases the resistance of osteosarcoma cells to doxorubicin by up-regulating the levels of multidrug resistance (MDR) 1 protein expression, and suggest the role of proteolytically released CD44 intracellular domain, and hyaluronan interactions in this process. Moreover, high throughput sequencing analysis identified differential regulation of several apoptosis-related genes in Cd44-positive and -negative primary osteosarcomas, including p53 apoptosis effector related to PMP-22 (Perp). Deletion of Cd44 in osteosarcoma cells led to doxorubicin-dependent p53 activation and a profound increase in Perp mRNA expression. Overall, our results suggest that CD44 might be an important regulator of drug resistance and suggest that targeting CD44 can sensitize osteosarcoma to standard chemotherapy.

Looking behind the choice of organic: A cross-country analysis applying Integrated Choice and Latent Variable Models.

This cross-country study investigates the relative role of organic labelling in consumers' purchase decisions for apples and the extent to which behavioral constructs, derived from an extension of the Theory of Planned Behavior, influence consumers' choices. We apply an Integrated Choice and Latent Variable Model, combining a discrete choice experiment with structural equation modelling. Empirical validation draws on data from an online survey conducted in three European countries (NGermany=404; NNorway=407; NUK=401). In all countries, price is by far the most important attribute in consumers' purchase decision of apples, followed by country-of-origin and production method. The results show considerable consistency across the investigated countries regarding the importance of behavioral constructs - attitudes, subjective norms, perceived behavioral control, trust, and personal moral norms - in explaining consumers' intentions to buy, and purchase choices for, organic apples, confirming the derived theoretical framework.

Cluster of differentiation 44 promotes osteosarcoma progression in mice lacking the tumor suppressor Merlin.

Merlin is a versatile tumor suppressor protein encoded by the NF2 gene. Several lines of evidence suggest that Merlin exerts its tumor suppressor activity, at least in part, by forming an inhibitory complex with cluster of differentiation 44 (CD44). Consistently, numerous NF2 mutations in cancer patients are predicted to perturb the interaction of Merlin with CD44. We hypothesized that disruption of the Merlin-CD44 complex through loss of Merlin, unleashes putative tumor- or metastasis-promoting functions of CD44. To evaluate the relevance of the Merlin-CD44 interaction in vivo, we compared tumor growth and progression in Cd44-positive and Cd44-negative Nf2-mutant mice. Heterozygous Nf2-mutant mice were prone to developing highly metastatic osteosarcomas. Importantly, while the absence of the Cd44 gene had no effect on the frequency of primary osteosarcoma development, it strongly diminished osteosarcoma metastasis formation in the Nf2-mutant mice. In vitro assays identified transendothelial migration as the most prominent cellular phenotype dependent on CD44. Adhesion to endothelial cells was blocked by interfering with integrin α4ß1 (very late antigen-4, VLA-4) on osteosarcoma cells and CD44 upregulated levels of integrin VLA-4 ß1 subunit. Among other putative functions of CD44, which may contribute to the metastatic behavior, the passage through the endothelial cells also appears to be critical in vivo, as CD44 significantly promoted formation of lung metastasis upon intravenous injection of osteosarcoma cells into immunocompromised mice. Altogether, our results strongly suggest that CD44 plays a metastasis-promoting role in the absence of Merlin.

Application of patient-derived liver cancer cells for phenotypic characterization and therapeutic target identification.

Primary liver cancer (PLC) ranks among the most lethal solid cancers worldwide due to lack of effective biomarkers for early detection and limited treatment options in advanced stages. Development of primary culture models that closely recapitulate phenotypic and molecular diversities of PLC is urgently needed to improve the patient outcome. Long-term cultures of 7 primary liver cancer cell lines of hepatocellular and cholangiocellular origin were established using defined culture conditions. Morphological and histological characteristics of obtained cell lines and xenograft tumors were analyzed and compared to original tumors. Time course analyses of transcriptomic and genomic changes were performed using next-generation sequencing (NGS). Key oncogenic alterations were identified by targeted NGS and cell lines carrying potentially actionable mutations were treated with corresponding specific inhibitors. PDCL fully resembled morphological features of the primary cancers in vitro and in vivo over extended period in culture. Genomic alterations as well as transcriptome profiles showed high similarity with primary tumors and remained stable during long-term culturing. Targeted-NGS confirmed that key oncogenic mutations such as TP53, KRAS, CTNNB1 as well as actionable mutations (e.g. MET, cKIT, KDR) were highly conserved in PDCL and amenable for individualized therapeutic approaches. Integrative genomic and transcriptomic approaches further demonstrated that PDCL more closely resemble molecular and prognostic features of PLC than established cell lines and are valuable tool for direct target evaluation. Our integrative analysis demonstrates that PDCL represents refined model for discovery of relevant molecular subgroups and exploration of precision medicine approaches for the treatment of this deadly disease.

Does the distribution frequency matter? A subgroup specific analysis of the effectiveness of the EU School Fruit and Vegetable Scheme in Germany comparing twice and thrice weekly deliveries.

OBJECTIVE: The present study aimed to examine the effectiveness of two different implementation forms of the EU School Fruit and Vegetable Scheme (SFVS). DESIGN: A quasi-experimental design was applied including a thrice as well as a twice weekly intervention group. Repeated 24 h dietary recalls were used to measure children's fruit and vegetable (F&V) intake. Effects were analysed on days with and without F&V deliveries using hierarchical linear regression models. SETTING: Twelve primary schools in North Rhine-Westphalia, Germany. SUBJECTS: Third and fourth graders (n 664). RESULTS: Average daily F&V intake at pre-intervention was 0·84 frequencies in the thrice weekly intervention group, 0·90 frequencies in the twice weekly intervention group and 1·25 frequencies in the control group. Providing children thrice weekly with F&V increased children's F&V intake on average by 0·96 (P<0·001) frequencies/d. The effects were higher on days with (1·07; P<0·001) than on days without (0·75; P<0·001) F&V deliveries. Distributing F&V twice weekly resulted in an increase of 0·75 (P<0·001) frequencies/d on average, again with higher effects on days with (1·30; P<0·001) than without (0·48; P<0·003) F&V deliveries. Subgroup analysis revealed some indications for differential effectiveness only in the twice weekly intervention group. CONCLUSIONS: The SFVS with thrice or twice weekly deliveries of F&V led to a significant increase in children's F&V intake on days with and without deliveries. The latter might provide an indication of positive long-term effects of the scheme. The scheme shows equal efficiency for almost all subgroups.

What determines the fruit and vegetables intake of primary school children? - An analysis of personal and social determinants.

The high prevalence of childhood obesity is a major concern in developed and developing countries. An increase in fruit and vegetable (F&V) intake is perceived as one of the numerous strategies to prevent and reduce the risk of adiposity. The purpose of this study was to investigate the relevance of personal and social determinants in explaining children's F&V intake. Written questionnaire data were collected from 702 parent-child pairs that included 3rd and 4th graders (aged 7 to 10) and their parents. Children's F&V intake was recorded over three food records. Hierarchical linear regression models were applied to assess the impact of personal and social determinants on children's F&V intake. Regression models focusing on personal and social determinants revealed that the most promising personal determinants pertained to the knowledge of different types of F&V and preferences for F&V. Moreover, an exclusive focus on social determinants indicated that parental modeling and peer influence had significant and positive relationships with children's F&V intake, whereas verbal directives to eat F&V exhibited a significant and negative relationship. In combination, the following four personal and social determinants were demonstrated to be significant: knowledge of different types of F&V, preferences for F&V and parental modeling, all of which had positive relationships, and verbal directives to eat F&V, which had a negative impact. The results identify important associative determinants of children's F&V intake. These are in part personal and in part social and are shown by our analysis to be of equal and perhaps mutual importance. Therefore, we suggest that interventions aimed at improving children's F&V intake should address children's preferences for F&V, impart knowledge concerning the variety of F&V and encourage parents to act as role models.

Who decides when to cleave an ectodomain?

Many life-essential molecules such as growth factors, cytokines, ectoenzymes, and decoy receptors are produced by ectodomain cleavage of transmembrane precursor molecules. Not surprisingly, misregulation of such essential functions is linked to numerous diseases. Ectodomain cleavage is the function of transmembrane ADAMs (a disintegrin and metalloprotease) and other membrane-bound metalloproteases, which have an extracellular catalytic domain. Almost all work on ectodomain cleavage regulation has focused on the control of enzyme activity determined by substrate cleavage as surrogate. However, the number of substrates far exceeds the number of enzymes. Specificity can therefore not be achieved by solely modulating enzyme activity. Here, we argue that specific regulatory pathways must exist to control the availability and susceptibility of substrates.

The European School Fruit Scheme: impact on children's fruit and vegetable consumption in North Rhine-Westphalia, Germany.

OBJECTIVE: To assess the impact of the European School Fruit Scheme (SFS) in North Rhine-Westphalia, Germany, on children's fruit and vegetable (F&V) consumption, in particular frequency. DESIGN: The study consisted of a pre-test/post-test design with an intervention (eight primary schools) and a control group (two primary schools). Children's F&V consumption frequency was measured prior to the introduction of the SFS in 2010 and after one year's delivery of F&V (2011). SETTING: Ten primary schools in North Rhine-Westphalia, Germany. SUBJECTS: In total, 499 primary-school children aged 6-11 years, 390 in the intervention and 109 in the control schools. RESULTS: Children highly appreciated the SFS. More than 90 % evaluated the programme positively. Children in the intervention group showed a significant increase in F&V intake frequency from baseline to follow-up, from on average 1·26 (sd 1·37) to 2·02 (sd 1·33) times/d (P=0·000). The intervention variable had a highly significant impact on children's F&V consumption frequency, even after controlling for gender, age and stay at school for lunch (ß=0·773; 95 % CI 0·59, 0·96). The SFS did not induce a reduction of F&V consumption at home. In the control group a non-significant decline in F&V consumption frequency from 1·31 (sd 1·26) to 1·18 (sd 1·34) times/d (P=0·325) was observed. CONCLUSION: One year after the programme's implementation, the SFS led to a significant short-term increase in children's F&V consumption.

What makes people leave their food? The interaction of personal and situational factors leading to plate leftovers in canteens.

In order to provide a basis for the reduction of food losses, our study analyzes individual food choice, eating and leftover behavior in a university canteen by consideration of personal, social and environmental determinants. Based on an extended literature review, a structural equation model is derived and empirically tested for a sample of 343 students. The empirical estimates support the derived model with a good overall model fit and sufficient R2 values for dependent variables. Hence, our results provide evidence for a general significant impact of behavioral intention and related personal and social determinants as well as for the relevance of environmental/situational determinants such as portion sizes and palatability of food for plate leftovers. Moreover, we find that environmental and personal determinants are interrelated and that the impact of different determinants is relative to perceived time constraints during a visit of the university canteen. Accordingly, we conclude that simple measures to decrease avoidable food waste may take effects via complex and interrelated behavioral structures and that future research should focus on these effects to understand and change food leftover behavior.

Children's purchase behavior in the snack market: Can branding or lower prices motivate healthier choices?

BACKGROUND: Children's dietary-related diseases and their associated costs have expanded dramatically in many countries, making children's food choice a policy issue of increasing relevance. As children spend a considerable amount of money on energy-dense, nutrient-poor (EDNP) products, a better understanding of the main drivers of children's independent food purchase decisions is crucial to move this behavior toward healthier options. OBJECTIVE: The objective of the study is to investigate the role of branding and price in motivating children to choose healthier snack options. METHODS: The study investigates snack choices of children ages 8 to 11, using a survey and a purchase experiment. The research took place in after-school programs of selected schools in the Boston area. Participants included 116 children. Products in the choice experiment differed on three factors: product type, brand, and price. Data were analyzed using aggregated and mixed logit models. RESULTS: Children's purchase decisions are primarily determined by product type (Importance Value (IV) 56.6%), while brand (IV 22.8%) and price (IV 20.6%) prove to be of less relevance. Only those children who state that they like the familiar brand reveal a preference for the branded product in their purchase decision. Price is a significant predictor of choice when controlling for whether or not children obtain an allowance. CONCLUSION: It is not simple brand awareness but a child's liking of the brand that determines whether a brand is successful in motivating a child to choose a product. The extent of children's experience with money influences their price responsiveness. To the extent that children who receive an allowance are primarily the ones buying food snacks, higher prices for EDNP snacks could be successful in motivating children to choose a healthier option.

Inside-out Regulation of Ectodomain Cleavage of Cluster-of-Differentiation-44 (CD44) and of Neuregulin-1 Requires Substrate Dimerization.

Ectodomain shedding of transmembrane precursor proteins generates numerous life-essential molecules, such as epidermal growth factor receptor ligands. This cleavage not only releases the regulatory growth factor, but it is also the required first step for the subsequent processing by γ-secretase and the release of gene regulatory intracellular fragments. Signaling within the cell modifies the cytoplasmic tails of substrates, a step important in starting the specific and regulated cleavage of a large number of studied substrates. Ectodomain cleavage occurs, however, on the outside of the plasma membrane and is carried out by membrane-bound metalloproteases. How the intracellular domain modification communicates with the ectodomain of the substrate to allow for cleavage to occur is unknown. Here, we show that homodimerization of a cluster-of-differentiation-44 or of pro-neuregulin-1 monomers represents an essential pre-condition for their regulated ectodomain cleavage. Both substrates are associated with their respective metalloproteases under both basal or cleavage-stimulated conditions. These interactions only turn productive by specific intracellular signal-induced intracellular domain modifications of the substrates, which in turn regulate metalloprotease access to the substrates' ectodomain and cleavage. We propose that substrate intracellular domain modification induces a relative rotation or other positional change of the dimerization partners that allow metalloprotease cleavage in the extracellular space. Our findings fill an important gap in understanding substrate-specific inside-out signal transfer along cleaved transmembrane proteins and suggest that substrate dimerization (homo- or possibly heterodimerization) might represent a general principle in ectodomain shedding.

Regulated ADAM17-dependent EGF family ligand release by substrate-selecting signaling pathways.

Ectodomain cleavage of cell-surface proteins by A disintegrin and metalloproteinases (ADAMs) is highly regulated, and its dysregulation has been linked to many diseases. ADAM10 and ADAM17 cleave most disease-relevant substrates. Broad-spectrum metalloprotease inhibitors have failed clinically, and targeting the cleavage of a specific substrate has remained impossible. It is therefore necessary to identify signaling intermediates that determine substrate specificity of cleavage. We show here that phorbol ester or angiotensin II-induced proteolytic release of EGF family members may not require a significant increase in ADAM17 protease activity. Rather, inducers activate a signaling pathway using PKC-α and the PKC-regulated protein phosphatase 1 inhibitor 14D that is required for ADAM17 cleavage of TGF-α, heparin-binding EGF, and amphiregulin. A second pathway involving PKC-δ is required for neuregulin (NRG) cleavage, and, indeed, PKC-δ phosphorylation of serine 286 in the NRG cytosolic domain is essential for induced NRG cleavage. Thus, signaling-mediated substrate selection is clearly distinct from regulation of enzyme activity, an important mechanism that offers itself for application in disease.

Health-related on-pack communication and nutritional value of ready-to-eat breakfast cereals evaluated against five nutrient profiling schemes.

BACKGROUND: There is an ongoing debate regarding health-related on-pack information appearing on products with low nutritional quality. The purpose of the study was to contribute to this discussion by examining the relationship between health-related on-pack information and the overall nutritional value of highly processed ready-to-eat breakfast cereals (RTECs). METHODS: Maximum variation sampling was used to select 128 highly processed RTECs in Germany in 2010. In 2012, two additional samples were collected in Norway (n =38) and Germany (n =73) to allow for comparisons of products from countries with different regulations concerning nutrient profiles. All products were evaluated against five nutrient profiling models from government-related agencies. Mann-Whitney U Tests and Chi-square statistics was used to compare the nutrient profiles of different product categories. Logistic regression analysis was conducted to identify on-pack information on German products predicting a satisfactory nutritional profile. RESULTS: The majority of RTECs displayed health-related information on the packaging, but only 4-36% of German products met the criteria of the different nutrient profiles. The rate was lower for cereals marketed to children, Norwegian cereals performed better (36-64%). Health-related on-pack information was not consistently related to the nutrient profiles. The following on-pack criteria predicted a satisfactory nutrient profile on RTECs of the German 2010 sample: i) cereals not marketed to children, ii) clean labelling (free-from claims) and possibly organic labelling and whole grain claims. CONCLUSIONS: Our results suggest that the implementation of a mandatory nutrient profiling scheme for products with health-related on-pack information could contribute to a consistent relationship between health-related information on RTECs and the overall nutritional value of the product. Improvements should also consider the provision of a simple nutritional labelling scheme on the front of the packaging, standardized serving sizes, accurate product names, and clearly defined whole grain claims.

Addressing ethnic disparities in neurological research in the United Kingdom: An example from the prospective multicentre COVID-19 Clinical Neuroscience Study.

BACKGROUND: Minority ethnic groups have often been underrepresented in research, posing a problem in relation to external validity and extrapolation of findings. Here, we aimed to assess recruitment and retainment strategies in a large observational study assessing neurological complications following SARS-CoV-2 infection. METHODS: Participants were recruited following confirmed infection with SARS-CoV-2 and hospitalisation. Self-reported ethnicity was recorded alongside other demographic data to identify potential barriers to recruitment. RESULTS: 807 participants were recruited to COVID-CNS, and ethnicity data were available for 93.2%. We identified a proportionate representation of self-reported ethnicity categories, and distribution of broad ethnicity categories mirrored individual centres' catchment areas. White ethnicity within individual centres ranged between 44.5% and 89.1%, with highest percentage of participants with non-White ethnicity in London-based centres. Examples are provided how to reach potentially underrepresented minority ethnic groups. CONCLUSIONS: Recruitment barriers in relation to potentially underrepresented ethnic groups may be overcome with strategies identified here.

Triggering cognitive dissonance with textual information and images: Data from three experiments with meat-eaters.

This article presents data from three experiments in which we triggered and measured cognitive dissonance in meat-eaters. Cognitive dissonance is a well-established concept in the social psychology literature; however, empirical measures are scarce. In all datasets, we used textual information and/or images related to meat consumption as means to trigger cognitive dissonance. Cognitive dissonance data was collected in Study 1 with a Likert scale, whereas Study 2 and 3 used a Semantic Bipolar scale. Each experiment was programmed with Qualtrics and consisted of four conditions. Data was collected online; Study 1 utilized social media to recruit participants while Study 2 and 3 were hosted on Prolific. All datasets contain items on participants' socio-demographic background, liking of different food products, cognitive dissonance, and a measure of meat avoidance. The data can be used to analyze the effect of information provision on cognitive dissonance and meat avoidance. Moreover, the relationship between socio-demographic variables and cognitive dissonance, as well as other exploratory purposes regarding meat avoidance can be explored. Furthermore, researchers can use the data to investigate differences between Likert scales and Semantic Bipolar scales. This data is related to the paper Can images and textual information lead to meat avoidance? The mediating role of cognitive dissonance[1].

Deletion of Cd44 Inhibits Metastasis Formation of Liver Cancer in Nf2-Mutant Mice.

Primary liver cancer is the third leading cause of cancer-related death worldwide. An increasing body of evidence suggests that the Hippo tumor suppressor pathway plays a critical role in restricting cell proliferation and determining cell fate during physiological and pathological processes in the liver. Merlin (Moesin-Ezrin-Radixin-like protein) encoded by the NF2 (neurofibromatosis type 2) gene is an upstream regulator of the Hippo signaling pathway. Targeting of Merlin to the plasma membrane seems to be crucial for its major tumor-suppressive functions; this is facilitated by interactions with membrane-associated proteins, including CD44 (cluster of differentiation 44). Mutations within the CD44-binding domain of Merlin have been reported in many human cancers. This study evaluated the relative contribution of CD44- and Merlin-dependent processes to the development and progression of liver tumors. To this end, mice with a liver-specific deletion of the Nf2 gene were crossed with Cd44-knockout mice and subjected to extensive histological, biochemical and molecular analyses. In addition, cells were isolated from mutant livers and analyzed by in vitro assays. Deletion of Nf2 in the liver led to substantial liver enlargement and generation of hepatocellular carcinomas (HCCs), intrahepatic cholangiocarcinomas (iCCAs), as well as mixed hepatocellular cholangiocarcinomas. Whilst deletion of Cd44 had no influence on liver size or primary liver tumor development, it significantly inhibited metastasis formation in Nf2-mutant mice. CD44 upregulates expression of integrin ß2 and promotes transendothelial migration of liver cancer cells, which may facilitate metastatic spreading. Overall, our results suggest that CD44 may be a promising target for intervening with metastatic spreading of liver cancer.