The Mas receptor has been reported to promote migration and invasion of clear cell renal cell carcinoma (ccRCC) cells via Ang-(1-7)-dependent AKT signaling. However, the mechanism underlying the regulation of Mas function remains unknown. Here, eight PDZ domain-containing proteins were identified as Mas interactors using surface plasmon resonance (SPR) coupled to mass spectrometry (MS). NHERF4 was the only downregulated gene across multiple independent ccRCC datasets. GST pull-down and co-immunoprecipitation assays confirmed physical interaction between NHERF4 and Mas. Using NHERF4 overexpression and knockdown assays, we found that NHERF4 inhibited Mas-induced migration, invasion and in vivo metastasis of ccRCC cells.  https://www.selleckchem.com/products/miransertib.html  Mechanistically, NHERF4 suppressed Mas-stimulated AKT phosphorylation and the PLC/Ca2+ response. We further demonstrated that NHERF4 compromised Mas-mediated migration and invasion of ccRCC cells via regulation of the PLC/AKT signaling axis. Analysis of the ccRCC dataset revealed that low levels of NHERF4 expression were correlated with higher TNM stage, and independently predicted poor prognosis of ccRCC patients. Overall, our study identified NHERF4 as a novel regulator of ccRCC invasiveness, and a prognostic biomarker, which may be beneficial for determining optimal therapeutic strategies for ccRCC patients.Pancreatic cancer is a malignancy with poor prognosis and high mortality. The recent increase in pancreatic cancer incidence and mortality has resulted in an increased number of studies on its epidemiology. This comprehensive and systematic literature review summarizes the advances in the epidemiology of pancreatic cancer, including its epidemiological trends, risk factors, risk prediction models, screening modalities, and prognosis. The risk factors for pancreatic cancers can be categorized as those related to individual characteristics, lifestyle and environment, and disease status. Several prediction models for pancreatic cancer have been developed in populations with new-onset diabetes or a family history of pancreatic cancer; however, these models require further validation. Despite recent progress in pancreatic cancer screening, the quantity and quality of related studies are also unsatisfactory, especially with respect to the identification of high-risk populations and development of effective screening modality. Apart from the populations with familial genetic risk and those at a high risk of sporadic pancreatic cancer, risk factors such as new-onset diabetes may be a new direction for timely intervention. We hope this work will provide new ideas for further prevention and treatment of pancreatic cancer.KRAS-mutant lung adenocarcinomas represent the largest molecular subgroup of non-small cell lung cancers (NSCLC) and are notorious for their dismal survival perspectives. To gain more insights in etiology and therapeutic response, we focused on the tumor suppressor Protein Phosphatase 2A (PP2A) as a player in KRAS oncogenic signaling. We report that the PP2A activator PTPA (encoded by PPP2R4) is commonly affected in NSCLC by heterozygous loss and low-frequent loss-of-function mutation, and this is specifically associated with poorer overall survival of KRAS-mutant lung adenocarcinoma patients. Reduced or mutant PPP2R4 expression in A549 cells increased anchorage-independent growth in vitro and xenograft growth in vivo, correlating with increased Ki67 and c-MYC expression. Moreover, KrasG12D-induced lung tumorigenesis was significantly accelerated in Ppp2r4 gene trapped mice as compared to Ppp2r4 wild-type. A confined kinase inhibitor screen revealed that PPP2R4-depletion induced resistance against selumetinib (MEK inhibitor), but unexpectedly sensitized cells for temsirolimus (mTOR inhibitor), in vitro and in vivo. Our findings underscore a clinically relevant role for PTPA loss-of-function in KRAS-mutant NSCLC etiology and kinase inhibitor response.ZEB1 is an important transcription factor that plays a critical role in TGF-β-induced epithelial-mesenchymal transition (EMT) and tumor metastasis. However, the mechanisms by which ZEB1 regulates metastasis in esophageal squamous cell carcinoma (ESCC) remain largely unknown. Here, we identified a novel circular RNA, circ-DOCK5, the biogenesis of which is directly regulated by ZEB1 and ZEB1-repressed RNA-binding protein eIF4A3. Tissue microarray analysis identified circ-DOCK5 to be downregulated in ESCC tissues, and its downregulation correlated with poor prognosis. Moreover, circ-DOCK5 increased the stability of miR-627-3p by functioning as a "reservoir" for miR-627-3p to partially reverse the ZEB1-enhanced migration and invasion in ESCC. MiR-627-3p inhibited the expression of TGFB2 and the secretion of TGF-β, which further resulted in downregulation of ZEB1 and suppression of TGF-β-induced EMT. In vivo experiments showed that ZEB1 promoted metastasis in ESCC by regulating expression of circ-DOCK5. Therefore, the present study revealed that ZEB1-mediated downregulation of circ-DOCK5 facilitates metastasis in ESCC by forming a positive feedback loop with TGF-β by altering the miR-627-3p/TGFB2 signaling. Targeting this signaling pathway may help suppress progression in ESCC.Humans show distinct social behaviours when we recognise social similarity in opponents that are members of the same social group. However, little attention has been paid to the role of social similarity in non-human animals. In the Wistar subject rats, the presence of an unfamiliar Wistar rat mitigated stress responses, suggesting the importance of social similarity in this stress-buffering phenomenon. We subsequently found that the presence of unfamiliar Sprague-Dawley (SD) or Long-Evans (LE) rats, but not an unfamiliar Fischer 344 (F344) rat, similarly mitigated stress responses in the subject rats. It is therefore possible that the subject rats recognised social similarity to unfamiliar SD and LE rats. In this study, we demonstrated that the Wistar subject rats were capable of categorizing unfamiliar rats based on their strain, and that the Wistar subjects showed a preference for unfamiliar Wistar, SD, and LE rats over F344 rats. However, the subject rats did not show a preference among Wistar, SD, and LE rats.