The trimeric coiled‐coil HSBP1 protein promotes WASH complex assembly at centrosomes

The Arp2/3 complex generates branched actin networks that exert pushing forces onto different cellular membranes. WASH complexes activate Arp2/3 complexes at the surface of endosomes and thereby fission transport intermediates containing endocytosed receptors, such as α5β1 integrins. How WASH complexes are assembled in the cell is unknown. Here, we identify the small coiled‐coil protein HSBP1 as a factor that specifically promotes the assembly of a ternary complex composed of CCDC53, WASH, and FAM21 by dissociating the CCDC53 homotrimeric precursor. HSBP1 operates at the centrosome, which concentrates the building blocks. HSBP1 depletion in human cancer cell lines and in Dictyostelium amoebae phenocopies WASH depletion, suggesting a critical role of the ternary WASH complex for WASH functions. HSBP1 is required for the development of focal adhesions and of cell polarity. These defects impair the migration and invasion of tumor cells. Overexpression of HSBP1 in breast tumors is associated with increased levels of WASH complexes and with poor prognosis for patients.     

Antimutagenicity of propionic acid bacteria]

The antimutagenicity of the cell extracts of Propionibacterium shermanii VKM-103, P. pentosaceum CCM 1859 and P. acnes CCM 3322 against mutagenicity of sodium azide and N-methyl-N'-nitro-N-nitrosoguanidine was demonstrated for the first time. The extracts of propionic acid cocci didn't show such effect. The antimutagenic factor acts as a desmutagen, has polypeptide nature and evidently is an enzyme (enzymes). The inhibitory effect of the extract is due to the presence of more than one protein factor in it.     

Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) Contributes to Tamoxifen Resistance in Estrogen-Positive Breast Cancer Patients

Molecular Biology - Crosstalk between the estrogen receptors and the receptor tyrosine kinases, including vascular endothelial growth factor receptor type II (VEGFR2), is a key mechanism in breast...     

Intratumor heterogeneity: Nature and biological significance

Intratumor heterogeneity inherent in the majority of human cancers is a major obstacle for a highly efficient diagnosis and successful prognosis and treatment of these diseases. Being a result of clonal diversity within the same tumor, intratumor heterogeneity can be manifested in variability of genetic and epigenetic status, gene and protein expression, morphological structure, and other features of the tumor. It is most likely that the appearance of this diversity is a source for the adaptation of the tumor to changes in microenvironmental conditions and/or a tool for changing its malignant potential. In any case, both processes result in the appearance of cell clones with different undetermined sets of hallmarks. In this review, we describe the heterogeneity of molecular disorders in various human tumors and consider modern viewpoints of its development including genetic and non-genetic factors of heterogeneity origin and the role of cancer stem cells and clonal evolution. We also systematize data on the contribution of tumor diversity to progression of various tumors and the efficiency of their treatment. The main problems are indicated in the diagnosis and therapy of malignant tumors caused by intratumor heterogeneity and possible pathways for their solution. Moreover, we also suggest the key goals whose achievement promises to minimize the problem of intratumor heterogeneity and to identify new prognostic, predictive, and target markers for adequate and effective treatment of cancer.