Apoptotic Signalling

Research group

Group Leader

Gabriel Gil Gómez

Dysregulation of DNA damage repair and signalling to cell cycle checkpoints is associated with a predisposition to cancer and affects responses to DNA-damaging anticancer therapy. We describe the role of Cyclin O in the regulation of DNA damage repair and in the activation of the cellular DNA damage checkpoints. Cyclin O is also a crucial regulator of the generation of multiciliated cells through modulation of the activity of the ciliogenic transcription factors FoxJ1 and Myb. It is also necessary for deuterosome-mediated centriole amplification and for apical docking of the basal bodies, the cilia-anchoring structures. Most human tumors show overexpression of Cyclin O. In vitro modification of cellular levels of Cyclin O leads to the generation of aberrant mitotic spindles due to centrosome amplification and to the appearance of stable polyploid cell clones. Our working hypothesis assumes that expression of Cyclin O in non-ciliated cells leads to deuterosome-mediated centriole amplification and consequent multipolar, aberrant mitotic spindle formation. Cyclin O expression in epithelial cells that have acquired a preneoplastic lesion as a consequence of the activation of the DNA damage response may be linked to the appearance of aneuploidy and genomic instability. Currently we are exploring the participation of Cyclin O in the transformation of preneoplasic lesions into full blown tumours.

 

2017

Members

Marta Garrido Saldaña (Technician)

 

Main Publications

• Sabbaghi M, Gil-Gómez G, Servitja S, Arpí O, García-Alonso S, Menéndez S, Arumí M, Serrano L, Salido M, Muntasell A, Martínez-García M, Zazo S, Chamizo C, González-Alonso P, Madoz-Gúrpide J, Eroles P, Arribas J, Tusquets I, Lluch A, Pandiella A, Rojo F, Rovira A, Albanell J. Defective cyclin B1 induction in trastuzumab-emtansine (T-DM1) acquired resistance in HER2-positive breast cancer. Clin Cancer Res 2017; 23(22): 7006-7019. IF 9.619. D1.

• Núñez M, Jung C, Terré B, Balsiger NA, Plata C, Roset R, Pardo-Pastor C, Garrido M, Rojas S, Alameda F, Lloreta J, Martín-Caballero J, Flores JM, Stracker TH, Valverde MA, Muñoz FJ, Gil-Gómez G. Constitutive Cyclin O deficiency results in penetrant hydrocephalus, impaired growth and infertility. Oncotarget 2017; 8(59): 99261-99273. IF 5.168. Q1.

Ongoing Research Projects

• Autoinmunidad, inflamación y cáncer: el papel mediador de la Ciclina O y su posible aplicación clínica como indicador temprano de transformación tumoral.

- Fondo de Investigación Sanitaria. ISCIII (PI13/00864)

- From 2014 to 2018

- Principal investigator: Gil Gómez, Gabriel

 

 

 

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