at the CNIC

Tag: cancer (Page 1 of 6)

Stress-activated kinases signaling pathways in cancer development

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.

JNK control of tumor microenvironment
JNK control of tumor microenvironment.

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.

Descubierto un mecanismo que controla la aparición del cáncer de hígado

Es un tumor silencioso. No avisa ni advierte de su presencia. Cuando se detecta suele ser ya demasiado tarde, porque el diagnóstico coincide con la colonización de otros órganos. La temida metástasis. Es el colangiocarcinoma, el segundo cáncer de hígado más común y uno de los más agresivos y con peor pronóstico de toda la amplia familia de tumores. Y es, también, uno de los grandes olvidados, porque la ciencia apenas ha descubierto nuevos tratamientos y ni tan siquiera lo conoce demasiado. Ha sido poco estudiado a nivel molecular, un vacío que ahora empieza a llenarse en parte con un descubrimiento realizado por investigadores del Centro Nacional de Investigaciones Cardiovasculares (CNIC), que han descubierto un mecanismo molecular que controla su aparición. El trabajo acaba de publicarse en la revista PNAS.

De izquierda a derecha: Alfonso Mora, Elena Rodríguez, Guadalupe Sabio, Alejandro Rosell, Cintia Folgueira y Luis Leiva-Vega.

JNK-mediated disruption of bile acid homeostasis promotes intrahepatic cholangiocarcinoma

Elisa Manieri, Cintia Folgueira, María Elena Rodríguez, Luis Leiva-Vega, Laura Esteban-Lafuente, Chaobo Chen, Francisco Javier Cubero, Tamera Barrett, Julie Cavanagh-Kyros, Davide Seruggia, Alejandro Rosell, Fátima Sanchez-Cabo, Manuel Jose Gómez, Maria J. Monte, Jose J. G. Marin, Roger J. Davis, Alfonso Mora & Guadalupe Sabio.

Obesity is associated with hepatic steatosis and activation of the cJun NH2-terminal kinase (JNK) stress-signaling pathway. Studies in mice demonstrate that JNK deficiency in the liver prevents the development of hepatic steatosis. This observation suggests that inhibition of JNK signaling may represent a possible treatment for hepatic steatosis. However, the long-term consequences of JNK inhibition are poorly understood.

Liver cholangiocarcinoma (Photo: Chaobo Chen).

Here we demonstrate that loss of JNK causes changes in cholesterol and bile acid metabolism that promote cholestasis, bile duct proliferation, and intrahepatic cholangiocarcinoma. We identify PPARα activation as the molecular mechanism that accounts for this phenotype .

Our analysis has important implications for the long-term use of JNK inhibitors for the treatment of obesity.

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