Colorectal cancer is among the leading causes of cancer-associated deaths worldwide. Treatment failure and tumor recurrence due to survival of therapy-resistant cancer stem/initiating cells represent major clinical issues to overcome. In this study, we identified lysine methyltransferase 9 (KMT9), an obligate heterodimer composed of KMT9α and KMT9β that monomethylates histone H4 at lysine 12 (H4K12me1), as an important regulator in colorectal tumorigenesis. KMT9α and KMT9β were overexpressed in colorectal cancer and colocalized with H4K12me1 at promoters of target genes involved in the regulation of proliferation. Ablation of KMT9α drastically reduced colorectal tumorigenesis in mice and prevented the growth of murine as well as human patient-derived tumor organoids. Moreover, loss of KMT9α impaired the maintenance and function of colorectal cancer stem/initiating cells and induced apoptosis specifically in this cellular compartment. Together, these data suggest that KMT9 is an important regulator of colorectal carcinogenesis, identifying KMT9 as a promising therapeutic target for the treatment of colorectal cancer. Significance: The H4K12 methyltransferase KMT9 regulates tumor cell proliferation and stemness in colorectal cancer, indicating that targeting KMT9 could be a useful approach for preventing and treating this disease.

ObjectiveFear of eye gaze and avoidance of eye contact are core features of social anxiety disorders (SAD). To measure self-reported fear and avoidance of eye gaze, the Gaze Anxiety Rating Scale (GARS) has been developed and validated in recent years in its English version. The main objectives of the present study were to psychometrically evaluate the German translation of the GARS concerning its reliability, factorial structure, and validity.MethodsThree samples of participants were enrolled in the study. (1) A non-patient sample (n = 353) completed the GARS and a set of trait questionnaires to assess internal consistency, test-retest reliability, factorial structure, and concurrent and divergent validity. (2) A sample of patients with SAD (n = 33) was compared to a healthy control group (n = 30) regarding their scores on the GARS and the trait measures.ResultsThe German GARS fear and avoidance scales exhibited excellent internal consistency and high stability over 2 and 4 months, as did the original version. The English version’s factorial structure was replicated, yielding two categories of situations: (1) everyday situations and (2) situations involving high evaluative threat. GARS fear and avoidance displayed convergent validity with trait measures of social anxiety and were markedly higher in patients with GSAD than in healthy controls. Fear and avoidance of eye contact in situations involving high levels of evaluative threat related more closely to social anxiety than to gaze anxiety in everyday situations.ConclusionsThe German version of the GARS has demonstrated reliability and validity similar to the original version, and is thus well suited to capture fear and avoidance of eye contact in different social situations as a valid self-report measure of social anxiety and related disorders in the social domain for use in both clinical practice and research.

<p>File with all the Supplementary Materials and Methods</p>

<p>File with all the Supplementary Figures (Supplementary Fig. S1-S4)</p>