RT info:eu-repo/semantics/doctoralThesis T1 Alterations in gene expression induced by oxaliplatin based chemotherapy in colorectal cancer A1 Rotoli, Deborah K1 Quimioterapia K1 Cáncer colorectal AB We analized the expression of the scaffold proteins IQGAP1, FKBP51 and AmotL2 and the Na,K-ATPase a and ß subunits in colorectal cancer and liver metastases after the administration of oxaliplatin-based chemotherapy. Double immuno-fluorescence protein localization, along with specific cell markers, on human cancer tissue specimens, showed that the expression levels and the subcellular redistribution of IQGAP1, FKBP51 and AmotL2 proteins in CRC cells and related metastases, are indicative of their involvement in CRC tumorigenesis, progression and EMT process. The co-localization of the three proteins with CD34 and/or CD31 in several cell vessels suggests their involvement in tumour angiogenesis and/or in vascular invasion. Due to the key role that these scaffold proteins exert in the dynamics of tumor cells, they represent an attractive group of interacting proteins that could be used as biomarkers for diagnostic staging and as targets for therapy. The expression pattern and localization of the a and ß subunits of the Na,K-ATPase is also affected in CRC, in metastases and in metastasized liver tissue. The a1, a3 and ß1 isoforms are the most highly expressed in tumour cells and metastases. The high levels of perinuclear and cytoplasmic a3 isoform detected in malignant liver tissues, suggests moonlighting functions for this isoform, besides ion transport. The possible predominant isozymes present in tumour and metastatic cells are a1ß1 and a3ß1, which exhibit the highest and lowest sodium ion affinity respectively, and the highest potassium ion affinity. These isozymes are likely to favor optimal conditions for the function of nuclear enzymes involved in mitosis, suggesting a possible role for this isozyme as a novel biomarker for CRC metastatic cells in liver. YR 2017 FD 2017 LK http://riull.ull.es/xmlui/handle/915/6824 UL http://riull.ull.es/xmlui/handle/915/6824 LA en NO Doctorado en Ciencias Médicas DS Repositorio institucional de la Universidad de La Laguna RD 13-dic-2024