Chemoresistance is a major problem in cancer therapy as cancer cells develop mechanisms that counteract the effect of chemotherapeutic compounds, leading to relapse and the development of more aggressive cancers that contribute to poor prognosis and survival rates of treated patients. Cancer stem cells (CSCs) play a key role in this event. Apart from their slow proliferative property, CSCs have developed a range of cellular processes that involve drug efflux, drug enzymatic inactivation and other mechanisms. In addition, the microenvironment where CSCs evolve (CSC niche), effectively contributes to their role in cancer initiation, progression and chemoresistance. In the CSC niche, immune cells, mesenchymal stem cells (MSCs), endothelial cells and cancer associated fibroblasts (CAFs) contribute to the maintenance of CSC malignancy via the secretion of factors that promote cancer progression and resistance to chemotherapy. Due to these factors that hinder successful cancer therapies, CSCs are a subject of intense research that aims at better understanding of CSC behaviour and at developing efficient targeting therapies. In this review, we provide an overview of cancer stem cells, their role in cancer initiation, progression and chemoresistance, and discuss the progress that has been made in the development of CSC targeted therapies.

Cell biologists generally consider that microtubules and actin play complementary roles in long- and short-distance transport in animal cells. On the contrary, using melanosomes of melanocytes as a model, we recently discovered that the motor protein myosin-Va works with dynamic actin tracks to drive long-range organelle dispersion in opposition to microtubules. This suggests that in animals, as in yeast and plants, myosin/actin can drive long-range transport. Here, we show that the SPIRE-type actin nucleators (predominantly SPIRE1) are Rab27a effectors that co-operate with formin-1 to generate actin tracks required for myosin-Va-dependent transport in melanocytes. Thus, in addition to melanophilin/myosin-Va, Rab27a can recruit SPIREs to melanosomes, thereby integrating motor and track assembly activity at the organelle membrane. Based on this, we suggest a model in which organelles and force generators (motors and track assemblers) are linked, forming an organelle-based, cell-wide network that allows their collective activity to rapidly disperse the population of organelles long-distance throughout the cytoplasm.

We have used proteomic fingerprinting to investigate diagnosis of Alzheimer's disease (AD). Samples of lumbar cerebrospinal fluid (CSF) from clinically-diagnosed AD cases (n = 33), age-matched controls (n = 20), and mild cognitive impairment (MCI) pa

Epithelial–mesenchymal transition (EMT) is a key event that is involved in the invasion and dissemination of cancer cells. Although typically considered as having tumour-suppressive properties, transforming growth factor (TGF)-β signalling is altered during cancer and has been associated with the invasion of cancer cells and metastasis. In this study, we report a previously unknown role for the cytoplasmic promyelocytic leukaemia (cPML) tumour suppressor in TGF-β signalling-induced regulation of prostate cancer-associated EMT and invasion. We demonstrate that cPML promotes a mesenchymal phenotype and increases the invasiveness of prostate cancer cells. This event is associated with activation of TGF-β canonical signalling pathway through the induction of Sma and Mad related family 2 and 3 (SMAD2 and SMAD3) phosphorylation. Furthermore, the cytoplasmic localization of promyelocytic leukaemia (PML) is mediated by its nuclear export in a chromosomal maintenance 1 (CRM1)-dependent manner. This was clinically tested in prostate cancer tissue and shown that cytoplasmic PML and CRM1 co-expression correlates with reduced disease-specific survival. In summary, we provide evidence of dysfunctional TGF-β signalling occurring at an early stage in prostate cancer. We show that this disease pathway is mediated by cPML and CRM1 and results in a more aggressive cancer cell phenotype. We propose that the targeting of this pathway could be therapeutically exploited for clinical benefit.