Tissue transglutaminase-mediated chemoresistance in cancer cells

摘要: Drug resistance and metastasis are major impediments for the successful treatment of cancer. A common feature among drug resistant metastatic tumor cells is that they exhibit profound to apoptosis. This property enables cancer not only grow survive in stressful environments (metastasis) but also display against many anticancer agents. Therefore, perturbation intrinsic apoptotic pathways will affect their ability respond chemotherapy metastasize distant sites. Recent studies have demonstrated cell lines selected chemotherapeutic drugs or isolated from sites, express elevated levels multifunctional protein, tissue transglutaminase (TG2). TG2 most diverse ubiquitous member family proteins implicated play a role apoptosis, wound healing, migration, attachment, growth, angiogenesis, matrix assembly. can associate with certain beta members integrin (beta1, beta3, beta4, beta5) promote stable interaction between extracellular (ECM), resulting increased survival, invasion. Additionally, forms ternary complex IkappaB/p65:p50 results constitutive activation nuclear transcription factor-kappaB (NF-kappaB). Moreover, expression leads focal adhesion kinase (FAK) its downstream PI3K/Akt survival pathway. Importantly, inhibition endogenous by small interfering RNA (siRNA) resulted reversal invasive phenotype. Conversely, ectopic promoted motility functions cells. review discusses current thinking implications development