Cyclin D1 (Ccnd1) together with its binding partner Cdk4 act as a transcriptional regulator to control cell proliferation and migration, and abnormal Ccnd1·Cdk4 expression promotes tumour growth and metastasis. While different nuclear Ccnd1·Cdk4 targets participating in cell proliferation and tissue development have been identified, little is known about how Ccnd1·Cdk4 controls cell adherence and invasion. Here, we show that the focal adhesion component paxillin is a cytoplasmic substrate of Ccnd1·Cdk4. This complex phosphorylates a fraction of paxillin specifically associated to the cell membrane, and promotes Rac1 activation, thereby triggering membrane ruffling and cell invasion in both normal fibroblasts and tumour cells. Our results demonstrate that localization of Ccnd1·Cdk4 to the cytoplasm does not simply act to restrain cell proliferation, but constitutes a functionally relevant mechanism operating under normal and pathological conditions to control cell adhesion, migration and metastasis through activation of a Ccnd1·Cdk4-paxillin-Rac1 axis.

Cyclin D1 (Ccnd1) is a proto-oncogen amplified in many different cancers and nuclear accumulation of Ccnd1 is a characteristic of tumor cells. Ccnd1 activates the transcription of a large set of genes involved in cell cycle progress and proliferation. However, Ccnd1 also targets cytoplasmic proteins involved in the regulation of cell migration and invasion. In this work, we have analyzed by immunohistochemistry the localization of Ccnd1 in endometrial, breast, prostate and colon carcinomas with different types of invasion. The number of cells displaying membranous or cytoplasmic Ccnd1 was significantly higher in peripheral cells than in inner cells in both collective and pushing invasion patterns of endometrial carcinoma, and in collective invasion pattern of colon carcinoma. Also, the cytoplasmic localization of Ccnd1 was higher when tumors infiltrated as single cells, budding or small clusters of cells. To evaluate cytoplasmic function of cyclin D1, we have built a variant (Ccnd1-CAAX) that remains attached to the cell membrane therefore sequestering this cyclin in the cytoplasm. Tumor cells harboring Ccnd1-CAAX showed high levels of invasiveness and metastatic potential compared to those containing the wild type allele of Ccnd1. However, Ccnd1-CAAX expression did not alter proliferative rates of tumor cells. We hypothesize that the role of Ccnd1 in the cytoplasm is mainly associated with the invasive capability of tumor cells. Moreover, we propose that subcellular localization of Ccnd1 is an interesting guideline to measure cancer outcome.

The COVID‐19 crisis in Spain has exacerbated the shortage of nursing staff to respond to increasing healthcare demands. For this reason, nursing students were requested to collaborate voluntarily as auxiliary health staff. This emergency has led to mental health problems in health professionals, hence the relevance of coping techniques. The objectives of this study were to explore the experiences and emotional responses of final‐year nursing students who volunteered to carry out healthcare relief tasks during the peak of the COVID‐19 pandemic, and to identify the coping strategies they adopted to deal with this situation. A qualitative study was conducted in the constructivist paradigm. Purposive sampling was used, and twenty‐two students participated in semi‐structured interviews, which were then content‐analysed. The study is reported using the COREQ checklist. Five themes emerged in the ‘Experiences and emotional response’ dimension (context, patients, emotions and feelings, risk of contagion, and personal satisfaction), and three themes emerged in the ‘Coping strategies’ dimension strategies in the work environment, in daily life and personal life. Although the students expressed negative emotions due to the highly complex context and lack of professional experience, they evaluated the experience positively in terms of learning and usefulness. Most notably, the students employed adaptive coping strategies to deal with the pandemic.