Leticia Herrera-Melle, María Crespo, Magdalena Leiva & Guadalupe Sabio.
Cancer is a large group of diseases characterized by abnormal cell growth that can lead to metastasis. It is the second leading cause of death worldwide, and its incidence is expected to rise over the next decades. Stress-activated protein kinases (SAPK) are important players in its regulation. Several studies have tried to unravel their role; however, their pro-tumorigenic or anti-tumorigenic properties are sometimes controversial.
In this review, we will discuss the main roles of the different SAPK in the control of tumor development through essential processes such as cell proliferation, apoptosis or invasiveness. We will also show the latest discoveries regarding the contribution of SAPK in shaping tumor microenvironment through the regulation of organ crosstalk and immune cell response during cancer progression.
All these studies are relevant examples of how SAPK offer new therapeutic avenues for cancer patients that may help increase their survival.
Elisa Manieri, Leticia Herrera-Melle, Alfonso Mora, Antonia Tomás-Loba, Luis Leiva-Vega, Delia I. Fernández, Elena Rodríguez, Laura Morán, Lourdes Hernández-Cosido, Jorge L. Torres, Luisa M. Seoane, Francisco Javier Cubero, Miguel Marcos & Guadalupe Sabio.
Hepatocellular carcinoma (HCC) is the sixth most common cancer type and the fourth leading cause of cancer-related death. This cancer appears with higher incidence in men and during obesity; however, the specific mechanisms underlying this correlation are unknown.
HCC gender differences are driven by adiponectin (Image: Leticia Herrera-Melle).
Adipose tissue, a key organ in metabolic syndrome, shows evident gender disparities in the production of adipokines. Levels of the important adipokine adiponectin decrease in men during puberty, as well as in the obese state. Here, we show that this decrease in adiponectin levels is responsible for the increased liver cancer risk in males. We found that testosterone activates the protein JNK in mouse and human adipocytes. JNK-mediated inhibition of adiponectin secretion increases liver cancer cell proliferation, since adiponectin protects against liver cancer development through the activation of AMP-activated protein kinase (AMPK) and p38α.
This study provides insight into adipose tissue to liver crosstalk and its gender relation during cancer development, having the potential to guide strategies for new cancer therapeutics
As in previous years, our group is open to master and advanced undergraduate students for extending their scientific training through hands-on experience in our laboratory during the summer recess (1 July – 30 September). In addition to carrying out a supervised research project, the students will also attend CNIC seminars.
The aim of the CICERONE program is to give university students first-hand knowledge of biomedical research so that they can make more informed choices about the possibility of pursuing a scientific career.
For the 2019 call, we are offering the following research projects:
Role of p38MAPK in metabolic diseases: Metabolic syndrome is a medical disorder defined by the co‐occurrence of obesity, impaired glucose tolerance, dyslipidemia and hypertension. Stress activated protein kinases have been shown to control both obesity by itself and diabetes associated to obesity. These stress kinases are activated by several MAPK activated kinases (MKK). We want to investigate the role of MKK3 in this process and the molecular mechanism by which this kinase could affect diabetes.
p38MAPK in heart physiology: The p38MAPK pathway transduces a variety of extracellular signals regulating cellular responses to stress, being implicated in cell proliferation, differentiation and apoptosis. Its implication in the development of human diseases it is being deeply studied. Four p38MAPK family members have been identified: p38α, β, γ and δ. Preliminary data from our laboratory show that these kinases may control cytokine production during acute and chronic inflammatory processes. Moreover, studies with genetically modified mice made in our laboratory confirm that p38MAPKs have a role in the development of the heart. Our main objective is to determine if the regulation of the p38MAPK signalling pathway could have beneficial effects in the cardiac response to exercise.