A5080827385- Genetic factors in colorectal cancer
- Colorectal Cancer Treatments and Studies
- Colorectal and Anal Carcinomas
- Cancer Genomics and Diagnostics
- Cancer-related gene regulation
- Cancer Cells and Metastasis
- Wnt/β-catenin signaling in development and cancer
- Axon Guidance and Neuronal Signaling
- Cancer, Hypoxia, and Metabolism
- Digestive system and related health
- Breast Cancer Treatment Studies
- Lung Cancer Treatments and Mutations
- Cancer-related Molecular Pathways
- Molecular Biology Techniques and Applications
- Breast Lesions and Carcinomas
- Cancer therapeutics and mechanisms
- Chromatin Remodeling and Cancer
- Hedgehog Signaling Pathway Studies
- Gastric Cancer Management and Outcomes
- Cancer-related molecular mechanisms research
- Multiple and Secondary Primary Cancers
- Hippo pathway signaling and YAP/TAZ
- AI in cancer detection
- Neuroblastoma Research and Treatments
- HER2/EGFR in Cancer Research
Memorial Sloan Kettering Cancer Center
2020-2025
Kettering University
2022-2024
Universitat Autònoma de Barcelona
2012-2024
Vall d'Hebron Institut de Recerca
2015-2024
Hebron University
2006-2023
Molecular Oncology (United States)
2006-2023
Justus-Liebig-Universität Gießen
2014-2023
CIBBIM-Nanomedicine
2006-2022
Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine
2009-2015
Heidelberg University
2010
CDH1 (E-cadherin) bi-allelic inactivation is the hallmark alteration of breast invasive lobular carcinoma (ILC), resulting in its discohesive phenotype. A subset ILCs, however, lack genetic/epigenetic inactivation, and their genetic underpinning unknown. Through clinical targeted sequencing data reanalysis 364 primary we identified 25 ILCs lacking alterations. promoter methylation was frequent (63%) these cases. Targeted revealed 3 harboring AXIN2 deleterious fusions (n = 2) or...
Abstract The family of receptor tyrosine kinases EPH and their Ephrin ligands regulate cell proliferation, migration, attachment. An important role in colorectal carcinogenesis is emerging for some its members. In this study, we evaluate the EPHB4 cancer value as a prognostic marker. levels were assessed by immunohistochemical staining tissue microarrays 137 tumors aberrant hypermethylation promoter was investigated using methylation-specific PCR. We found that expression frequently reduced...
Abstract Solid tumours are exposed to microenvironmental factors such as hypoxia that normally inhibit cell growth. However, tumour cells capable of counteracting these signals through mechanisms largely unknown. Here we show the prolyl hydroxylase PHD3 restrains growth in response cues control EGFR. silencing human gliomas or genetic deletion a murine high-grade astrocytoma model markedly promotes and ability continue growing under unfavourable conditions. The growth-suppressive function is...
Abstract Inherited MYO5B mutations have recently been associated with microvillus inclusion disease (MVID), an autosomal recessive syndrome characterized by intractable, life-threatening, watery diarrhea appearing shortly after birth. Characterization of the molecular mechanisms underlying this and development novel therapeutic approaches is hampered lack animal models. In study we describe phenotype a mouse model targeted inactivation Myo5b . knockout mice show perinatal mortality,...
The loss of the epithelial architecture and cell polarity/differentiation is known to be important during tumorigenic process. Here we demonstrate that brush border protein Myosin Ia (MYO1A) for polarization differentiation colon cancer cells frequently inactivated in colorectal tumors by genetic epigenetic mechanisms. MYO1A frame-shift mutations were observed 32% (37 116) with microsatellite instability analyzed, evidence promoter methylation was a significant proportion lines primary...
Tumours exploit their hypoxic microenvironment to induce a more aggressive phenotype, while curtailing the growth-inhibitory effects of hypoxia through mechanisms that are poorly understood. The prolyl hydroxylase PHD3 is regulated by and plays an important role in tumour progression. Here we identify as central regulator epidermal growth factor receptor (EGFR) activity control EGFR internalization restrain growth. controls acting scaffolding protein associates with endocytic adaptor Eps15...
Lung cancer is the leading cause of cancer-related death worldwide, in large part due to its high propensity metastasize and develop therapy resistance. Adaptive responses hypoxia epithelial-mesenchymal transition (EMT) are linked tumor metastasis drug resistance, but little known about how oxygen sensing EMT intersect control these hallmarks cancer. Here, we show that sensor PHD3 links hypoxic signaling regulation lung microenvironment. was repressed by signals induce acted as a negative...
Abstract Sclerosing stromal tumor (SST) of the ovary is a rare type sex cord-stromal (SCST), whose genetic underpinning currently unknown. Here, using whole-exome, targeted capture and RNA-sequencing, we report recurrent FHL2-GLI2 fusion genes in 65% (17/26) SSTs other GLI2 rearrangements additional 15% (4/26) SSTs, none which are detected types SCSTs ( n = 48) or common cancer 9,950). The fusions result transcriptomic activation Sonic Hedgehog (SHH) pathway SSTs. Expression vitro leads to...
Abstract Colorectal cancer is the second cause of cancer-related death in western world, and although genetic molecular mechanisms involved initiation progression these tumors are among best characterized, there significant gaps our understanding this disease. The role EPHB signaling colorectal has only recently been realized. Here, we use animal models to investigate EphB4 intestinal tumorigenesis. Modulation EPHB4 levels colon cell lines resulted differences tumor growth a xenograft model,...
Artificial intelligence (AI) systems can improve cancer diagnosis, yet their development often relies on subjective histologic features as ground truth for training. Herein, we developed an AI model applied to whole-slide images using CDH1 biallelic mutations, pathognomonic invasive lobular carcinoma (ILC) in breast neoplasms, truth. The accurately predicted mutations (accuracy = 0.95) and diagnosed ILC 0.96). A total of 74% samples classified by the having but lacking these alterations...
Abstract Metaplastic breast cancers (MBCs) are characterized by complex genomes, which seem to vary according their histologic subtype. TERT promoter hotspot mutations and gene amplification rare in common forms of cancer, but present a subset phyllodes tumors. Here, we sought determine the frequency genetic alterations affecting cohort 60 MBCs with distinct predominant metaplastic components (squamous, 23%; spindle, 27%; osseous, 8%; chondroid, 42%), compare repertoire presence or...
Abstract Although deregulation of EPHB signaling has been shown to be an important step in colorectal tumorigenesis, the role EPHB6 this process not investigated. We found here that manipulation levels colon cancer cell lines no effect on their motility and growth a solid substrate, soft agar or xenograft mouse model. then used EphB6 knockout model show inactivation does efficiently initiate tumorigenesis intestinal tract. In addition, when tumors are initiated genetically pharmacologically...
The clinical management of colorectal cancer patients has significantly improved because the identification novel therapeutic targets such as EGFR and VEGF. Because rapid tumor proliferation is associated with poor patient prognosis, here we characterized transcriptional signature rapidly proliferating cells in an attempt to identify candidate targets.The doubling time 52 cell lines was determined genome-wide expression profiling a subset these assessed by microarray analysis. We then...
Reduced RHOA signalling has been shown to increase the growth/metastatic potential of colorectal tumours. However, mechanisms inactivation in colon cancer have not characterised. A panel cell lines and large cohorts primary tumours were used investigate expression activity RHOA, as well presence mutations/deletions promoter methylation affecting RHOA. Changes assessed by western blotting qPCR after modulation microRNAs, SMAD4 c-MYC. We show here that point mutations hypermethylation do...
Mixed invasive ductal and lobular carcinoma (MDLC) is a rare histologic subtype of breast cancer displaying both E-cadherin positive negative morphologies within the same tumor, posing challenges with regard to anticipated clinical management. It remains unclear whether these distinct also have biology risk recurrence. Our spatially resolved transcriptomic, genomic, single-cell profiling revealed clinically significant differences between tumor regions including intrinsic heterogeneity –...
Colorectal cancers (CRC) with microsatellite instability (MSI) have clinical, pathologic, genetic, and epigenetic features distinct from microsatellite-stable CRC. Examination of epidermal growth factor receptor (EGFR) mRNA protein expression levels in a panel colon cancer cell lines identified strong EGFR multiple MSI. Although no relationship between overexpression the length CA dinucleotide repeat intron 1 was observed, variant A13/A14 sequence within 3'-untranslated region (3'-UTR) gene...
Abstract Purpose: Irinotecan (CPT11) treatment significantly improves the survival of colorectal cancer patients and is routinely used for these patients, alone or in combination with other agents. However, only 20% to 30% show an objective response irinotecan, there great need new molecular markers capable identifying subset who are unlikely respond. Experimental Design: Here we microarray analysis a panel 30 cell lines immunohistochemistry identify validate biomarker irinotecan. Results: A...