Metastasis causes death of 90% of cancer patients, so it is the most significant issue associated with cancer disease. Thus, it is no surprise that many researchers are trying to develop drugs targeting or preventing them. The secondary tumour site formation is closely related to phenomena like epithelial-to-mesenchymal and its reverse, mesenchymal-to-epithelial transition. The change of the cells’ phenotype to mesenchymal involves the acquisition of migratory potential. Cancer cells movement is possible due to the development of invasive structures like invadopodia, lamellipodia, and filopodia. These changes are dependent on the reorganization of the actin cytoskeleton. In turn, the polymerization and depolymerization of actin are controlled by actin-binding proteins. In many tumour cells, the actin and actin-associated proteins are accumulated in the cell nucleus, suggesting that it may also affect the progression of cancer by regulating gene expression. Once the cancer cell reaches a new habitat it again acquires epithelial features and thus proliferative activity. Targeting of epithelial-to-mesenchymal or/and mesenchymal-to-epithelial transitions through regulation of their main components expression may be a potential solution to the problem of metastasis. This work focuses on the role of these processes in tumour progression and the assessment of therapeutic potential of agents targeting them.

The actin cytoskeleton plays a crucial role in many cellular processes while its reorganization is important in maintaining cell homeostasis. However, in the case of cancer cells, actin and ABPs (actin-binding proteins) are involved in all stages of carcinogenesis. Literature has reported that ABPs such as SATB1 (special AT-rich binding protein 1), WASP (Wiskott-Aldrich syndrome protein), nesprin, and villin take part in the initial step of carcinogenesis by regulating oncogene expression. Additionally, changes in actin localization promote cell proliferation by inhibiting apoptosis (SATB1). In turn, migration and invasion of cancer cells are based on the formation of actin-rich protrusions (Arp2/3 complex, filamin A, fascin, α-actinin, and cofilin). Importantly, more and more scientists suggest that microfilaments together with the associated proteins mediate tumor vascularization. Hence, the presented article aims to summarize literature reports in the context of the potential role of actin and ABPs in all steps of carcinogenesis.

Metastasis is one of the most urgent issues in breast cancer patients. One of the factors necessary in the migration process is the remodeling of the extracellular matrix (ECM). Metalloproteinases (MMPs) can break down the elements of the ECM, which facilitates cell movement. Many highly aggressive tumors are characterized by high levels of MMPs. In the case of breast cancer, the association between MMP-9 and the migration potential and invasiveness of cells has been demonstrated. In addition, reports indicating increased migration of breast cancer cells after the administration of the commonly used cytostatic cyclophosphamide (CP) are particularly disturbing. Hence, our research aimed to assess the effect of CP treatment on MDA-MB-231 and MCF-7 cells and how this response is influenced by the downregulation of the MMP-9 level. The obtained results suggest that CP causes a decrease in the survival of breast cancer cells of various invasiveness, and the downregulation of MMP-9 enhances this effect, mainly by inducing apoptosis. Moreover, in the group of MMP-9 siRNA-transfected CP-treated cells, a more severe reduction in invasion and migration of cells of both lines was observed, as indicated by the migration and invasion transwell assays and Wound healing assay. Hence, we suggest that CP alone may not result in satisfactory therapeutic effects. On the other hand, the use of combination therapy targeting MMP-9, together with the CP, could improve the effectiveness of the treatment. Additionally, we confirmed a relationship between the levels of MMP-9 and cytokeratin 19 (CK19).

Lamins are the major components of the nuclear lamina and play important roles in many cellular processes. The role of lamins in cancer development and progression is still unclear but it is known that reduced expression of lamin B1 has been observed in colon cancer. Thus, the aim of the present study was to elucidate the influence of LMNB1 upregulation on colon cancer cell line after treatment with 5-FU. The results indicate, that overexpression of LMNB1 induced dose-dependent cell death mainly by mitotic catastrophe pathway. Furthermore, after upregulation of this intermediate protein, lower expression of lamin A/C was observed. Moreover, we observed an increase in fluorescence intensity of nuclear β-catenin and decrease in cell-cell interaction area, that was connected with inhibition of colon cancer cells migration. We present the reorganization of actin filament and β-tubulin, because these cytoskeletal proteins are directly or indirectly linked with lamins, and analyzing publicly available mRNA data we show that patients with overexpression of LMNB1 are characterized by lower survival rates within the first 30 months from diagnosis. Summarizing our results, upregulation of LMNB1 induce mitotic catastrophe and only small percentage of apoptosis. Moreover, we showed inhibition of cell migration and promotion of cell-cell contact as a results of direct and indirect regulation of β-catenin, lamin A/C, actin and tubulin. However, it is possible that mitotic catastrophe cells in patients with colorectal cancer may be a reservoir of the cells responsible for faster disease progression, and further investigations are necessary to confirm this hypothesis.

Background: Cancers are one of the leading causes of deaths nowadays. The development of new treatment schemes for oncological diseases is an interesting direction in experimental medicine. Therefore, the evaluation of the influence of two alkaloids—piperlongumine (PL), sanguinarine (SAN) and their combination—on the basic life processes of the A549 cell line was considered reasonable. Methods: The aim was achieved by analyzing the cytotoxic effects of PL and SAN and their combination in the ratio of 4:1 on the induction of cell death, changes in the distribution of cell cycle phases, reorganization of cytoskeleton and metastatic potential of A549 cells. The versatility of the applied concentration ratio was evaluated in terms of other cancer cell lines: MCF-7, H1299 and HepG2. Results: The results obtained from the MTT assay indicated that the interaction between the alkaloids depends on the concentration and type of cells. Additionally, the compounds and their combination did not exhibit a cytotoxic effect against normal cells. The combined effects of PL and SAN increased apoptosis and favored metastasis inhibition. Conclusion: Selected alkaloids exhibit a cytotoxic effect on A549 cells. In turn, treatment with the combination of PL and SAN in a 4:1 ratio indicates a synergistic effect and is associated with an increase in the level of reactive oxygen species (ROS).