About the VHIR
Here at the Vall d'Hebron Research Institute (VHIR) we promote biomedical research, innovation and teaching. Over 1,800 people are seeking to understand diseases today so the treatment can be improved tomorrow.
We are working to understand diseases, to find out how they operate and to create better treatments for patients. Get to know about our groups and their lines of research.
People are the centre of the Vall d'Hebron Research Institute (VHIR). This is why we are bound by the principles of freedom of research, gender equality and professional attitudes that HRS4R promotes.
Our work is not just basic or translational; we are leaders in clinical research. Enter and find about the clinical trials we are conducting and why we are a world reference in this field.
Our aim is to make the research carried out at the Vall d’Hebron Research Institute (VHIR) a driving force for transformation. How? By identifying new channels and solutions for the promotion of people's health and well-being.
We offer specialist support for researchers, internal and external alike, ranging from specific services to preparing complete projects. All this, from a perspective of quality and speed of response.
We offer you a gateway for staying up to date on everything going on at the Vall d’Hebron Research Institute (VHIR), from the latest news to future solidarity activities and initiatives that we are organising.
Dra. Nora Diéguez Martínez, Protein kinases and cancer research group (VHIR)
Endometrial cancer (EC) is the most common type of gynaecological cancer in women of developed countries. Despite surgery combined with chemo-/radiotherapy regimens, overall survival of patients with high-risk EC tumors is poor, indicating a need for novel therapies. The MEK5-ERK5 pathway is activated in response to growth factors and to different stressors, including oxidative stress and cytokines. Previous evidence supports a role for the MEK5-ERK5 pathway in the pathology of several cancers. We investigated the role of ERK5 in EC. In silico analysis of the PanCancer Atlas dataset showed alterations in components of the MEK5-ERK5 pathway in 48% of EC patients. Here, we show that ERK5 inhibition or silencing decreased EGF-induced EC cell proliferation, and that genetic deletion of MEK5 resulted in EC impaired proliferation and reduced tumor growth capacity in nude mice. Pharmacologic inhibition or ERK5 silencing impaired NF-kB pathway in EC cells and xenografts. Furthermore, we found a positive correlation between ERK5 and p65/RELA protein levels in human EC tumor samples. Mechanistically, genetic or pharmacologic impairment of ERK5 resulted in downregulation of NEMO/IKKg expression, leading to impaired p65/RELA activity and to apoptosis in EC cells and xenografts, which was rescued by NEMO/IKKg overexpression. Notably, ERK5 inhibition, MEK5 deletion or NF-kB inhibition sensitized EC cells to standard EC chemotherapy (paclitaxel/carboplatin) toxicity, whereas ERK5 inhibition synergized with paclitaxel to reduce tumor xenograft growth in mice. Together, our results suggest that the ERK5-NEMO-NF-kB pathway mediates EC cell proliferation and survival. We propose the ERK5/NF-kB axis as new target for EC treatment.
Host: Dr. José Miguel Lizcano de Vega, Protein kinases and cancer research group (VHIR)