Background & Aims: Due to their inherent characteristics, the function of group-2 innate lymphoid cells (ILC2s) varies in a context-dependent manner. ILC2s are involved in certain liver diseases; however, their involvement in hepatocellular carcinoma (HCC) is unknown. In the present study, we assessed the role of an HCC-derived ILC2 population in tumor progression.

Among hundreds of thousands of signal receptors contributing to oncogenic activation, tumorigenesis, and metastasis, the hepatocyte growth factor (HGF) receptor-also called tyrosine kinase MET-is a promising target in cancer therapy as its axis is involved in several different cancer types. It is also associated with poor outcomes and is involved in the development of therapeutic resistance. Several HGF/MET-neutralizing antibodies and MET kinase-specific small molecule inhibitors have been developed, resulting in some context-dependent progress in multiple cancer treatments. Nevertheless, the concomitant therapeutic resistance largely inhibits the translation of such targeted drug candidates into clinical application. Until now, numerous studies have been performed to understand the molecular, cellular, and upstream mechanisms that regulate HGF/METtargeted drug resistance, further explore novel strategies to reduce the occurrence of resistance, and improve therapeutic efficacy after resistance. Intriguingly, emerging evidence has revealed that, in addition to its conventional function as an oncogene, the HGF/MET axis stands at the crossroads of tumor autophagy, immunity, and microenvironment. Based on current progress, this review summarizes the current challenges and simultaneously proposes future opportunities for HGF/MET targeting for therapeutic cancer interventions.

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Introduction: Previous epidemiological studies have found an increased risk for ischemic stroke in patients with migraine; however, the evidence for a causal relationship between migraine and ischemic stroke is scarce. This study aims to explore the potential causal relationship between migraine and ischemic stroke and its subtypes [including large artery stroke (LAS), small vessel stroke (SVS), and cardioembolic stroke (CES)]. Methods: We used data on genetic variants associated with migraine identified from a genome-wide association study (GWAS) metaanalysis among 889,018 European ancestries. Summary data for ischemic stroke and its subtypes were obtained from the MEGASTROKE consortium including up to 438,847 participants. We performed two-sample Mendelian randomization (MR) analyses using the inversevariance-weighted method as the primary approach. The MR-Egger, weighted median, simple median, simple mode, and weighted mode methods were also conducted as sensitivity analyses to determine the robustness of our results. Results: We failed to detect statistically significant associations between migraine and ischemic stroke (OR, 0.935; 95% CI 0.851-1.027; P = 0.159) and its subtypes (LAS: OR, 0.818; 95% CI 0.692-0.967; P = 0.018) (SVS: OR, 0.935; 95% CI 0.781-1.119; P = 0.460) (CES: OR, 1.015; 95% CI 0.867-1.189; P = 0.850). The results were consistent with the sensitivity analyses. Conclusions: By conducting a series of causal inference approaches, this study supports no causal effect of migraine on ischemic stroke and its subtypes.