Filopodia and stromal extracellular matrix as regulators of cancer cell invasion and growth

Bidirectional exchange of information between the cancer cells and their environment is essential for cancer to evolve. Cancer cells lose the ability to regulate their growth, gain the ability to detach from neighboring cells and finally some of the cells disseminate from the primary tumor and invade to the adjacent tissue. During cancer progression, cells acquire features that promote cancer motility and proliferation one of them being increased filopodia number. Filopodia are dynamic actin-rich structures extending from the leading edge of migrating cells and the main function of these structures is to serve as environmental sensors. It is nowadays widely appreciated, that not only the cancer cells, but also the surrounding of the tumor – the tumor microenvironment- contribute to cancer cell dissemination and tumor growth. Activated stromal fibroblasts, also known as cancer-associated fibroblasts (CAFs) actively participate on tumor progression. CAFs are the most abundant cell type surrounding the cancer cells and they are the main cell type producing the extracellular matrix (ECM) within tumor stroma. CAFs secrete growth factors to promote tumor growth, direct cancer cell invasion as well as modify the stromal ECM architecture. The aim of this thesis was to investigate the function of filopodia, particularly the role of filopodia-inducing protein Myosin-X (Myo10), in breast cancer cell invasion and metastasis. We found that Myo10 is an important regulator of basal type breast cancer spreading downstream of mutant p53. In addition, I investigated the role of CAFs and their secreted matrix on tumor growth. According to the results, CAF-derived matrix has altered organization and stiffness which induces the carcinoma cell proliferation via epigenetic mechanisms. I identified histone demethylase enzyme JMJD1a to be regulated by the stiffness and to participate in stiffness induced growth control.

The Role of HR Management in the Corporate Matrix System

The successful performance of company in the market relates to the quality management of human capital aiming to improve the company's internal performance and external implementation of the core business strategy. Companies with matrix structure focusing on realization and development of innovation and technologies for the uncertain market need to select thoroughly the approach to HR management system. Human resource management has a significant impact on the organization and use a variety of instruments such as corporate information systems to fulfill their functions and objectives. There are three approaches to strategic control management depending on major impact on the major interference in employee decision-making, development of skills and his integration into the business strategy. The mainstream research has focus only on the framework of strategic planning of HR and general productivity of firm, but not on features of organizational structure and corporate software capabilities for human capital. This study tackles the before mentioned challenges, typical for matrix organization, by using the HR control management tools and corporate information system. The detailed analysis of industry producing and selling electromotor and heating equipment in this master thesis provides the opportunity to improve system for HR control and displays its application in the ERP software. The results emphasize the sustainable role of matrix HR input control for creating of independent project teams for matrix structure who are able to respond to various uncertainties of the market and use their skills for improving performance. Corporate information systems can be integrated into input control system by means of output monitoring to regulate and evaluate the processes of teams, using key performance indicators and reporting systems.