Aplicación de Proteómica a la búsqueda de nuevos mecanismos tumorales en cáncer de tiroides

Comunicaciones a congreso

Functional insight into the reciprocal paracrine crosstalk of stromal fibroblasts in the head and neck cancer microenvironment

Trabajo presentado en el 18th ASEICA International Congress, celebrado en Santiago de Compostela (España) del 16 al 18 de noviembre de 2022

Exome sequencing of early-onset patients supports genetic heterogeneity in colorectal cancer

Colorectal cancer (CRC) is a complex disease that can be caused by a spectrum of genetic variants ranging from low to high penetrance changes, that interact with the environment to determine which individuals will develop the disease. In this study, we sequenced 20 early-onset CRC patients to discover novel genetic variants that could be linked to the prompt disease development. Eight genes, CHAD, CHD1L, ERCC6, IGTB7, PTPN13, SPATA20, TDG and TGS1, were selected and re-sequenced in a further 304 early onset CRC patients to search for rare, high-impact variants. Although we found a recurring truncating variant in the TDG gene shared by two independent patients, the results obtained did not help consolidate any of the candidates as promising CRC predisposing genes. However, we found that potential risk alleles in our extended list of candidate variants have a tendency to appear at higher numbers in younger cases. This supports the idea that CRC onset may be oligogenic in nature and may show molecular heterogeneity. Further, larger and robust studies are thus needed to unravel the genetics behind early-onset CRC development, coupled with novel functional analyses and omic approaches that may offer complementary insight

Revista de Vertebrados de la Estación Biológica de Doñana

Tiempo y orden de aparición de las escamas en el salmón del Atlántico (Salmo salar)Estudios sobre el sapo corredor (Bufo calamita) en el sur de España.III. ReproducciónInfluencia de las carecterísticas del medio acuático sobre las poblaciones de larvas de anfibios en lala Reserva Biológica de Doñana(Huelva, EspañaDieta de la cigüeñuela (Himantopus himantopus) en las salinas del estuario del GuadianaOrientación y selección del lugar del nido en el gorrión moruno (Passer hispaniolensis)la avifauna de las Vegas Bajas del Guadianala reproducción de la malvasía (Oxyura leucocephala) en el sur de la provincia de Córdoba, España.La alimentación de la curruca cabecinegra (Sylvia melanocephala, Gmelin 1788) en olivares de la provincia de Jaén (otoño-invierno)Consideraciones sobre el efecto de los conejos y los grandes herbívoros en los pastizales de la Vera de DoñanaAnálisis factorial de las expresiones faciales del babuino sagrado (Papio hamadryas)Contaminación xenobiótica del Parque Nacionalde Doñana. II. Residuos de insecticidas organoclorados, bifenilos policlorados, (PGBs) y metales pesados en Falconiformes y StrigiformesTransferencia total y del y bioacumulación de mercurio y metilmercurio en ecosistemas del Parque Nacional de DoñanaNota sobre la alimentación de larvas de anfibios: I. Pleurodeles waltl en charcas temporaleNota sobre nuevas especies parasitada por el críalo (Clamator glandarius) en EspañaEstructura de la jerarquización en la predación de huevos y pichones en Spheniscus magellanicusPasser domesticus, nueva specie para Bolivia¿Están realmente subalimentados los cernícalos primilla en el valle del Guadalquivir durante el periodo no reproductor?.Nidificación del paiño común (Hydrobates pelagicus) en las Islas Canarias.Nuevos datos sobre la presencia del visón europeo (Mustela lutreola L.) en NavarraLa población de gamos del Parque Nacional de Doñana en 1979Puntualización a la nota "predacción de Falco peregrino y Falco subbuteo sobre quirópteros" de Aymerich y García de Castro aparecida en el vol. 9 de esta revista.Peer reviewe

Cleavage of Fibulin-2 by the aggrecanases ADAMTS-4 and ADAMTS-5 contributes to the tumorigenic potential of breast cancer cells

Fibulin-2 participates in the assembly of extracellular matrix components through interactions with multiple ligands and promotes contacts between cells and their surrounding environment. Consequently, identification of processes that could lead to an altered Fibulin-2 could have a major impact not only in the maintenance of tissue architecture and morphogenesis but also in pathological situations including cancer. Herein, we have investigated the ability of the secreted metalloproteases ADAMTS-4 and ADAMTS-5 to digest Fibulin-2. Using in vitro approaches and cultured breast cancer cell lines we demonstrate that Fibulin-2 is a better substrate for ADAMTS-5 than it is for ADAMTS-4. Moreover, Fibulin-2 degradation is associated to an enhancement of the invasive potential of T47D, MCF-7 and SK-BR-3 cells. We have also found that conditioned medium from MCF-7 cells that simultaneously overexpress Fibulin-2 and ADAMTS-5 significantly induced the migratory and invasive ability of normal breast fibroblasts using 3D collagen matrices. Immunohistochemical analysis highlights the close proximity or partial overlap of both Fibulin-2 and ADAMTS-5 in breast tumor samples. Additionally, proteolytic products derived from a potential degradation of Fibulin-2 by ADAMTS-5 were also identified in these samples. Finally, we also show that the cleavage of Fibulin-2 by ADAMTS-5 is counteracted by ADAMTS-12, a metalloprotease that interacts with Fibulin-2. Overall, our results provide direct evidence indicating that Fibulin-2 is a novel substrate of ADAMTS-5 and that this proteolysis could alter the cellular microenvironment affecting the balance between protumor and antitumor effects associated to both Fibulin-2 and the ADAMTSs metalloproteases

Cleavage of Fibulin-2 by the aggrecanases ADAMTS-4 and ADAMTS-5 contributes to the tumorigenic potential of breast cancer cells

Fibulin-2 participates in the assembly of extracellular matrix components through interactions with multiple ligands and promotes contacts between cells and their surrounding environment. Consequently, identification of processes that could lead to an altered Fibulin-2 could have a major impact not only in the maintenance of tissue architecture and morphogenesis but also in pathological situations including cancer. Herein, we have investigated the ability of the secreted metalloproteases ADAMTS-4 and ADAMTS-5 to digest Fibulin-2. Using in vitro approaches and cultured breast cancer cell lines we demonstrate that Fibulin-2 is a better substrate for ADAMTS-5 than it is for ADAMTS-4. Moreover, Fibulin-2 degradation is associated to an enhancement of the invasive potential of T47D, MCF-7 and SK-BR-3 cells. We have also found that conditioned medium from MCF-7 cells that simultaneously overexpress Fibulin-2 and ADAMTS-5 significantly induced the migratory and invasive ability of normal breast fibroblasts using 3D collagen matrices. Immunohistochemical analysis highlights the close proximity or partial overlap of both Fibulin-2 and ADAMTS-5 in breast tumor samples. Additionally, proteolytic products derived from a potential degradation of Fibulin-2 by ADAMTS-5 were also identified in these samples. Finally, we also show that the cleavage of Fibulin-2 by ADAMTS-5 is counteracted by ADAMTS-12, a metalloprotease that interacts with Fibulin-2. Overall, our results provide direct evidence indicating that Fibulin-2 is a novel substrate of ADAMTS-5 and that this proteolysis could alter the cellular microenvironment affecting the balance between protumor and antitumor effects associated to both Fibulin-2 and the ADAMTSs metalloproteases

Bidirectional paracrine communication between head and neck cancer cells and stromal fibroblasts

Resumen del trabajo presentado en el European Association for Cancer Research (EACR) Congress, celebrado en Sevilla (España) del 20 al 23 de junio de 2023

Thyroid cancer GWAS identifies 10q26.12 and 6q14.1 as novel susceptibility loci and reveals genetic heterogeneity among populations

Thyroid cancer is the most heritable cancer of all those not displaying typical Mendelian inheritance. However, most of the genetic factors that would explain the high heritability remain unknown. Our aim was to identify additional common genetic variants associated with susceptibility to this disease. In order to do so, we performed a genome-wide association study in a series of 398 cases and 502 controls from Spain, followed by a replication in four well-defined Southern European case-control collections contributing a total of 1,422 cases and 1,908 controls. The association between the variation at the 9q22 locus near FOXE1 and thyroid cancer risk was consistent across all series, with several SNPs identified (rs7028661: OR = 1.64, p = 1.0 x 10(-22) , rs7037324: OR = 1.54, p = 1.2 x 10(-17) ). Moreover, the rare alleles of three SNPs (rs2997312, rs10788123 and rs1254167) at 10q26.12 showed suggestive evidence of association with higher risk of the disease (OR = 1.35, p = 1.2 x 10(-04) , OR = 1.26, p = 5.2 x 10(-04) and OR = 1.38, p = 5.9 x 10(-05) , respectively). Finally, the rare allele of rs4075570 at 6q14.1 conferred protection in the series studied (OR = 0.82, p = 2.0 x 10(-04) ). This study suggests that heterogeneity in genetic susceptibility between populations is a key feature to take into account when exploring genetic risk factors related to this disease