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.

β-Glucans are considered candidates for the medication in different human pathologies. In this work, we have purified β-glucan from a selected barley line and tested their effects in primary human dermal fibroblasts. Unexpectedly, we have observed that this compound promoted a short-transitory proliferation arrest at 24 h after its addition on the medium. We have determined that this transitory arrest was dependent on the cell-cycle regulator protein Retinoblastoma. Moreover, dermal fibroblasts increase their migration capacities at 24 h after barley β-glucan addition. Also, we have described that barley β-glucan strongly reduced the ability of fibroblasts to attach and to spread on cell plates. Our data indicates that barley β-glucan signal induces an early response in HDF cells favoring migration versus proliferation. This feature is consistent with our observation that the topical addition of our barley β-glucan in vivo accelerates the wound closure in mouse skin.

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.

Characterization of cytoplasmic cyclin D1 as a marker of invasiveness in cancer

Glioblastoma (GBM) is a highly invasive brain neoplasia with an elevated recurrence rate after surgical resection. The CyclinD1 (Ccnd1)/Cdk4–RB1 axis is frequently altered in GBM, leading to over‐proliferation by RB1 deletion or by Ccnd1/Cdk4 over‐activation. By not so well understood mechanisms, high levels of Ccnd1‐Cdk4 also promote GBM cell invasion. The purpose of this work is to elucidate the in vivo role of cytoplasmic Ccnd1‐Cdk4 activity in the dissemination of GBM. We show that Ccnd1 activates invasion of primary human GBM cells through cytoplasmic RB1‐independent mechanisms. By using GBM mouse models, we observed that evaded GBM cells showed cytoplasmic Ccnd1 co‐localizing with regulators of cell invasion such as RalA and Paxillin. Our genetic data strongly suggest that, in GBM cells, the Ccnd1/Cdk4 complex is acting upstream of those regulators. Accordingly, expression of Ccnd1 induces FAK, RalA and Rac1 activities. Finally, in vivo experiments demonstrated increased GBM dissemination after expression of membrane‐targeted Ccnd1. We conclude that Ccnd1‐Cdk4 activity promotes GBM dissemination through cytoplasmic and RB1‐independent mechanisms. Therefore, inhibition of Ccnd1‐Cdk4 activity may be useful to hinder dissemination of recurrent GBM.