#IDIBELLfellows: Gemma Gonfaus / Lucia del Carmen Gonzalez Alcocer

Role of the NADPH oxidase NOX4 in the regulation of Endoplasmic Reticulum (ES) stress in liver tumor cells
Gemma Gonfaus – TGF-beta and cancer group
In hepatic carcinogenesis, reactive oxygen species (ROS) generate an oxidative microenvironment promoting endoplasmic reticulum (ER) stress and hepatocyte cell death. Such conditions can impact on protein folding by inducing Unfolded Protein Response (UPR). The NADPH oxidase (NOX) family has been described to be an important source of ROS, being NOX1, NOX2 and NOX4 the main ones in the liver. Recent results from our group have described NOX4 as a regulator of redox homeostasis in Hepatocellular Carcinoma (HCC). We aim to study whether NOX4 expression in HCC cells modulates the cellular response towards an ER stress stimuli. We present loss- or gain-of-function of NOX4 in HCC cells where ER stress was induced with tunicamycin and thapsigargin. In basal conditions, we localized NOX4 in ER and mitochondria as well as demonstrated an increased size of mitochondria in NOX4 knock-down cells by transmission electron microscopy. Moreover, we observed that MAM contact sites were tighter in NOX4 knock-down cells whereas cells overexpressing NOX4 displayed the opposite effect. When analyzing the different branches of the UPR pathway we observed alterations in the PERK branch as levels of p-EIF2α and ATF4 activity were increased in NOX4 knock-down cells. Furthermore, we subjected NOX4-knock-down cells to ER stress and observed a significant decrease in OCR when compared to untreated conditions. Subsequently, we studied if this ER stress stimuli could lead to apoptosis and our results revealed that NOX4 knock-down cells had a significant increase in caspase-3 activity accompanied with increased cleaved PARP protein levels. Likewise, NOXA and PUMA expression levels were upregulated upon ER stress induction. Overall, HCC cells expressing high levels of NOX4 may be more protected against ER stress through the PERK pathway. Additionally, NOX4 might regulate the oxidative metabolism upon ER stress induction and play a potential role in protecting cells from undergoing apoptosis. 

Psychosocial and Sociodemographic Profiles of Breast Cancer Patients
Lucia del Carmen Gonzalez Alcocer – Psycho-oncology and digital health (PSODIG) group
Introduction: Receiving a Breast Cancer diagnosis is frequently perceived as a threatening experience (ref). Patients commonly experience anxiety, depression, distress, and post-traumatic stress. These symptoms often persist throughout their treatment and survivorship journey. Psychological treatments for those symptoms have demonstrated efficacy in early-stage cancer patients, but there are still many challenges related to access, dosage, and responsiveness. ICOnnecta’t is a stepped digital psychosocial health program designed and created to address these needs.
Aims: to identify the presence of recently diagnosed BC patient subgroups classified according to psychosocial, sociodemographic and clinical variables. Methods: This study follows an additional analysis of a larger multicentre randomized controlled trial (RCT) that evaluated the effectiveness of ICOnnecta`t.
Results: revealed the existence of three groups: Cluster 1 (Early stages and minimal distress, 61.7%) having least psychosocial impairment, Cluster 2 (Advanced Stages and Moderate Distress, 16.8%) included patients in advanced cancer stages and moderate psychological impairment. Cluster 3 (Distress and Growth in Early Stages, 21.6%) had the highest post-traumatic stress and psychological distress, but also showed significant post-traumatic growth. Emotional distress and cancer stage were the main discriminators between clusters, while sociodemographic variables showed limited relevance.