Aneuploidy renders cancer cells vulnerable to mitotic checkpoint inhibition

Selective targeting of aneuploid cells is an attractive strategy for cancer treatment(1). Here, we mapped the aneuploidy landscapes of ~1,000 human cancer cell lines, and analyzed genetic and chemical perturbation screens(2–9) to reveal aneuploidy-associated cellular vulnerabilities. We identified and validated an increased sensitivity of aneuploid cancer cells to genetic perturbation of core components of the spindle assembly checkpoint (SAC), which ensures the proper segregation of chromosomes during mitosis(10). Surprisingly, we also found aneuploid cancer cells to be less sensitive to short-term exposures to multiple SAC inhibitors. Indeed, aneuploid cancer cells became increasingly more sensitive to SAC inhibition (SACi) over time. Aneuploid cells exhibited aberrant spindle geometry and dynamics, and kept dividing in the presence of SACi, resulting in accumulating mitotic defects, and in unstable and less fit karyotypes. Therefore, although aneuploid cancer cells could overcome SACi more readily than diploid cells, their long-term proliferation was jeopardized. We identified a specific mitotic kinesin, KIF18A, whose activity was perturbed in aneuploid cancer cells. Aneuploid cancer cells were particularly vulnerable to KIF18A depletion, and KIF18A overexpression restored their response to SACi. Our study reveals a novel, therapeutically-relevant, synthetic lethal interaction between aneuploidy and the SAC

Formation of senior students’ sociocultural competence by means of blog technology

This article is devoted to the research of the formation of sociocultural competence in the process of teaching a foreign language at the senior stage with the help of the blog technology. The relevance of this article is because sociocultural competence is one of the structural components of communicative competence, which is key in the context of global intercultural communication. The aim of the research is to provide the theoretical basis and practical verification of the effectiveness of using blog technology in the formation of the sociocultural competence of senior students in a foreign language class. In the research, the authors analysed the characteristics of the blog and the benefits of its use, revealed that using the blog technology can develop almost all types of speech activities: writing, reading and listening, as well as improve the sociocultural competence of students. Obviously, the blog technology has many advantages compared to other technologies, as it includes all types of information. Consequently, the blog provides an opportunity to implement various tasks. The article describes the experimental work, namely, its purpose, tasks, stages, conditions, content, methods of teaching the formation of the sociocultural competence of senior students

Mapping the landscape of genetic dependencies in chordoma

Cancer cells possess unique molecular features that can confer an increased dependence on specific genes. Here, the authors use CRISPR-Cas9 screens to identify selectively essential genes and therapeutic targets in chordoma