Sabio lab

at the CNIC

Tag: liver (page 1 of 6)

p38γ is essential for cell cycle progression and liver tumorigenesis

Antonia Tomás-Loba, Elisa Manieri, Bárbara González-Terán, Alfonso Mora, Luis Leiva-Vega, Ayelén M. Santamans, Rafael Romero-Becerra, Elena Rodríguez, Aránzazu Pintor-Chocano, Ferran Feixas, Juan Antonio López, Beatriz Caballero, Marianna Trakala, Óscar Blanco, Jorge L. Torres, Lourdes Hernández-Cosido, Valle Montalvo-Romeral, Nuria Matesanz, Marta Roche-Molina, Juan Antonio Bernal, Hannah Mischo, Marta León, Ainoa Caballero, Diego Miranda-Saavedra, Jesús Ruiz-Cabello, Yulia A. Nevzorova, Francisco Javier Cubero, Jerónimo Bravo, Jesús Vázquez, Marcos Malumbres, Miguel Marcos, Sílvia Osuna & Guadalupe Sabio.

The cell cycle is a tightly regulated process that is controlled by the conserved cyclin-dependent kinase (CDK)–cyclin protein complex. However, control of the G0-to-G1 transition is not completely understood.

Mitosis in liver
Mitosis in hepatocytes (Photo: Alfonso Mora/CNIC).

Here we demonstrate that p38 MAPK gamma (p38γ) acts as a CDK-like kinase and thus cooperates with CDKs, regulating entry into the cell cycle. p38γ shares high sequence homology, inhibition sensitivity and substrate specificity with CDK family members. In mouse hepatocytes, p38γ induces proliferation after partial hepatectomy by promoting the phosphorylation of retinoblastoma tumour suppressor protein at known CDK target residues.

Lack of p38γ or treatment with the p38γ inhibitor pirfenidone protects against the chemically induced formation of liver tumours. Furthermore, biopsies of human hepatocellular carcinoma show high expression of p38γ, suggesting that p38γ could be a therapeutic target in the treatment of this disease.

Investigar con perspectiva de género es básico para salvar la vida de las mujeres y prevenir enfermedades

A Guadalupe Sabio Buzo la ciencia le corre por las venas. Pero no es lo único. Sabe muy bien el esfuerzo que supone dedicarse a la investigación en un mundo copado por hombres. Por eso el suyo es el ejemplo de la sororidad allá donde las batas blancas y las probetas se unen. “Se están dando pasos para conseguir un sistema científico más igualitario tanto en instituciones europeas como en España. Pero, aunque es verdad que hemos mejorado y cada vez somos más las mujeres que llenamos los laboratorios de investigación, todavía nos falta mucho por hacer en los puestos de decisión. Se necesitan políticas activas hasta que se consiga la masa crítica suficiente para que el hecho de estar peor representadas en los puestos de decisión no se traduzca en que nos cueste más llegar a ellos”, explica.

[Read more in Público]

Guadalupe Sabio en la entrada del CNIC.

Adiponectin accounts for gender differences in hepatocellular carcinoma incidence

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.

Adiponectin accounts for gender differences in liver cancer

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

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