Purpose: Scalable solutions are needed to make pre-test genetic education about inherited cancer risk accessible across diverse and underserved populations. We evaluated an automated strategy to deliver genetic education through a web-based video among young Black females with breast cancer. Methods: 96 participants were recruited through state cancer registries in Florida and Tennesee. All participants viewed a 12 min video and completed a ten question quiz on inherited cancer knowledge before and after viewing the video. Median pre- and postvideo knowledge scores were categorized as <60% versus ≥60% and compared across demographic and clinical characteristics using binary logistic regression. Results: Of the 96 participants, mean age was 51, over 50% had income <$50 K, over 40% did not graduate college or have private insurance, and over 70% had previous genetic testing. Median knowledge scores significantly increased after viewing the video (p < 001), with no significant differences in those with or without prior testing. A higher post-video knowledge score was associated with an income ≥$50 K, a college degree, and private insurance (all p < .05). Conclusion: Among a population of young Black breast cancer patients, the educational video significantly increased knowledge. Findings support the use of automated pre-test educational tools as a scalable solution to make these services more accessible across populations.
Breast Neoplasms , Humans , Female , Middle Aged , Breast Neoplasms/genetics , Breast Neoplasms/epidemiology , Black People , Genetic Testing , Florida , Internet
Integrins - the principal extracellular matrix (ECM) receptors of the cell - promote cell adhesion, migration, and proliferation, which are key events for cancer growth and metastasis. To date, most integrin-targeted cancer therapeutics have disrupted integrin-ECM interactions, which are viewed as critical for integrin functions. However, such agents have failed to improve cancer patient outcomes. We show that the highly expressed integrin ß1 subunit is required for lung adenocarcinoma development in a carcinogen-induced mouse model. Likewise, human lung adenocarcinoma cell lines with integrin ß1 deletion failed to form colonies in soft agar and tumors in mice. Mechanistically, we demonstrate that these effects do not require integrin ß1-mediated adhesion to ECM but are dependent on integrin ß1 cytoplasmic tail-mediated activation of focal adhesion kinase (FAK). These studies support a critical role for integrin ß1 in lung tumorigenesis that is mediated through constitutive, ECM binding-independent signaling involving the cytoplasmic tail.
Adenocarcinoma of Lung , Adenocarcinoma , Lung Neoplasms , Adenocarcinoma/genetics , Adenocarcinoma of Lung/genetics , Animals , Humans , Integrin beta1/genetics , Integrin beta1/metabolism , Integrins , Ligands , Lung Neoplasms/pathology , Mice
BACKGROUND: SET domain-containing protein 2 (SETD2) is commonly mutated in renal cell carcinoma. SETD2 methylates histone H3 as well as a growing list of non-histone proteins. OBJECTIVE: Initially, we sought to explore SETD2-dependent changes in lysine methylation of proteins in proximal renal tubule cells. Subsequently, we focused on changes in lysine methylation of the translation elongation factor eEF1A1. METHODS: To accomplish these objectives, we initially performed a systems-wide analysis of protein lysine-methylation and expression in wild type (WT) and SETD2-knock out (KO) kidney cells and later focused our studies on eEF1A1 as well as the expression of lysine methyltransferases that regulate its lysine methylation. RESULTS: We observed decreased lysine methylation of the translation elongation factor eEF1A1. EEF1AKMT2 and EEF1AKMT3 are known to methylate eEF1A1, and we show here that their expression is dependent on SET-domain function of SETD2. Globally, we observe differential expression of hundreds of proteins in WT versus SETD2-KO cells, including increased expression of many involved in protein translation. Finally, we observe decreased progression free survival and loss of EEF1AKMT2 gene expression in SETD2-mutated tumors predicted to have loss of function of the SET domain. CONCLUSION: Overall, these data suggest that SETD2-mutated ccRCC, via loss of enzymatic function of the SET domain, displays dysregulation of protein translation as a potentially important component of the transformed phenotype.
