The GTPase Rac1 is a key component in the reorganization of the actin cytoskeleton that is induced by growth factors or oncogenic Ras1. Here we investigate the role of Rac1 in cell transformation and show that Rat1 fibroblasts expressing activated Val-12 Rac1 (Rac1 with valine at residue 12) display all the hallmarks of malignant transformation. In a focus-forming assay in NIH3T3 fibroblasts to measure the efficiency of transformation, we found that dominant-negative Asn-17 Rac1 inhibited focus formation by oncogenic Ras, but not by RafCAAX, a Raf kinase targeted to the plasma membrane by virtue of the addition of a carboxyterminal localization signal from K-Ras. This indicates that Rac is essential for transformation by Ras. In addition, Val-12 Rac1 synergizes strongly with RafCAAX in focus-formation assays, indicating that oncogenic Ras drives both the Rac and MAP-kinase pathways, which cooperate to cause transformation.

Results from 5 studies illustrate how perception of and experiences with low job mobility can shape culture-characteristic pattern of judgments and behaviors. Although both Americans and some Asian groups (e.g., Chinese, Asian Americans) consider having successful practitioners' personality traits (role personalities) to be important to job performance, the Asian groups place heavier emphasis on possessing role personalities when making performance forecast than do Americans (Studies 1-3). Moreover, even among Americans, a brief subjective experience with low job mobility can increase the perceived importance of possessing role personalities in performance forecast (Study 4), and a brief direct experience with low job mobility can increase job applicants' tendency to claim possession of role personality traits in job applications (Study 5). Furthermore, the belief in a fixed world mediates the relationship between perception of low job mobility and perceived importance of possessing role personalities in performance forecast (Study 2).

The physical and psychological condition of patients with gynaecological cancer has received much attention, but there is little research on spirituality in palliative care. This study aimed to investigate spiritual well-being and its association with quality of life, anxiety and depression in patients with gynaecological cancer. A cross-sectional study was conducted in China in 2019 with 705 patients diagnosed with primary gynaecological cancer. European Organisation for Research and Treatment of Cancer quality of life instruments (EORTC QLQ-SWB32 and EORTC QLQ-C30) and the Hospital Anxiety and Depression Scale were used to measure spiritual well-being, quality of life, anxiety and depression. Univariate and multiple linear regression analyses were performed to examine associations between spiritual well-being, quality of life, anxiety and depression. Functioning scales and global health status were positively correlated with spiritual well-being (P < .05). Anxiety and depression were negatively correlated with spiritual well-being (P < .05). Depression (−0.362, P < .001) was the strongest predictor of Existential score. Anxiety (−0.522, P < .001) was the only predictor of Relationship with self. Depression (−0.350, P < .001) and Global health (0.099, P = .011) were the strongest predictors of Relationship with others. Religion (−0.204, P < .001) and Depression (−0.196, P < .001) were the strongest predictors of Relationship with someone or something greater. Global health (0.337, P < .001) and Depression (−0.144, P < .001) were the strongest predictors of Global-SWB. Well spiritual well-being is associated with lower anxiety and depression, and better quality of life. Health providers should provide more spiritual care for non-religious patients and combine spiritual care with psychological counselling to help patients with gynaecological cancer, especially those who have low quality of life or severe symptoms, or experience anxiety or depression.

Summary Invadopodia are protrusive structures used by tumor cells for degradation of the extracellular matrix to promote invasion [1]. Invadopodia formation and function are regulated by cytoskeletal remodeling pathways and the oncogenic kinase Src. The guanine nucleotide exchange factor Vav1, which is an activator of Rho family GTPases, is ectopically expressed in many pancreatic cancers, where it promotes tumor cell survival and migration [2, 3]. We have now determined that Vav1 is also a potent regulator of matrix degradation by pancreatic tumor cells, as depletion of Vav1 by siRNA-mediated knockdown inhibits the formation of invadopodia. This requires the exchange function of Vav1 toward the GTPase Cdc42, which is required for invadopodia assembly [4, 5]. In addition, we have determined that Src-mediated phosphorylation and activation of Vav1 is both required for, and, unexpectedly, sufficient for, invadopodia formation. Expression of Vav1 Y174F, which mimics its activated state, is a potent inducer of invadopodia formation through Cdc42, even in the absence of Src activation and phosphorylation of other Src substrates, such as cortactin. Thus, these data identify a novel mechanism by which Vav1 can enhance the tumorigenicity and invasive potential of cancer cells. These data suggest that Vav1 promotes the matrix-degrading processes underlying tumor cell migration, and further, under conditions of ectopic Vav1 expression, that Vav1 is a central regulator and major driver of invasive matrix remodeling by pancreatic tumor cells.