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The role of cyclins in hormone-dependent neoplasms is crucial in the development of the disease that is resistant to first-line therapy, as the example of breast cancer shows. However, in prostate cancer, cyclins are studied to a lesser extent. There are some well-described molecular pathways, including cyclins A1 and D1 signaling, however the role of other cyclins, e.g., D2, D3, E, and H, still requires further investigation. Recent studies indicate that cyclins regulate various cellular processes, not only the cell cycle. Furthermore, they remain in cross-talk with many other signaling pathways, e.g., MAPK/ERK, PI3K/Akt, and Notch. The androgen signaling axis, which is pivotal in prostate cancer progression, interferes with cyclin pathways at many levels. This article summarizes current knowledge on the influence of cyclins on prostate cancer progression by describing interactions between the androgen receptor and cyclins, as well as mechanisms underlying the development of resistance to currently used therapies. [Display omitted] • Cyclins play a key role in the regulation of the cell cycle. • The androgen pathway interferes with cyclin signalling pathways at many levels. • The cyclins level may be a predictor of patient's prognosis • Some cyclins may act as a drug target in castration-resistant prostate cancer. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) and prostate cancer (PC) are at the top of the list when it comes to the most common types of cancers worldwide. The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway is important, in that it strongly influences the development and progression of these tumors. Previous studies have emphasized the key role of inhibitors of the PIK3/AKT/mTOR signaling pathway in the treatment of BC and PC, and it remains to be a crucial method of treatment. In this review, the inhibitors of these signaling pathways are compared, as well as their effectiveness in therapy and potential as therapeutic agents. The use of these inhibitors as polytherapy is evaluated, especially with the use of hormonal therapy, which has shown promising results. [Display omitted] • The PI3K/AKT/mTOR pathway is one of the most crucial signaling pathways in cells. • Mutations in this pathway commonly contribute to the development of breast and prostate cancer. • The inhibitors targeting the PI3K/AKT/mTOR signaling pathway represent promising therapeutic targets. • Polytherapy involving inhibitors, in conjunction with hormonal therapy, demonstrates encouraging outcomes. [ABSTRACT FROM AUTHOR]

This study aimed to investigate rapid effect of anti-androgen 2-hydroxyflutamide (HF) on cadherin/catenin complex and androgen receptor (AR) phosphorylation in prostate cancer cell lines. In addition, a role of PI3K/Akt and MAPK/ERK1/2 pathways in mediating these effects was explored. We have demonstrated that in androgen-sensitive LNCaP cells HF induced rapid increase of E-cadherin phosphorylation at Ser 838/840 (p < 0.05) in MAPK/ERK1/2-dependent manner, whereas phosphorylation of β-catenin at Tyr 654 was unchanged. Concomitantly, the reduction of the level of AR phosphorylated at Ser210/213 was found (p < 0.01). In androgen-independent PC3 cells HF decreased Tyr 860 N-cadherin and Tyr 645 β-catenin phosphorylation (p < 0.01), acting via both MAPK/ERK1/2 and PI3K/Akt pathways. Further, we evidenced that MAPK/ERK1/2 and PI3K/Akt pathways were differentially influenced by HF in LNCaP and PC3 cells. In LNCaP cells, both Akt (p < 0.01) and ERK1/2 (p < 0.001) phosphorylation were negatively regulated and this effect was mediated by Raf-1 (p < 0.05). In contrast, in PC3 cells HF stimulated Akt (p < 0.001) and ERK1/2 (p < 0.001) activation, but had no effect on the crosstalk between PI3K/Akt and MEK/ERK1/2 pathways at the Raf-1 kinase level. Our findings expand the role of anti-androgen into non-genomic signaling, creating a link between anti-androgen action and phosphorylation of adherens junction proteins in prostate cancer cells. [ABSTRACT FROM AUTHOR]

Melanoma is relatively resistant to chemotherapy, and no targeted therapies are fully effective. The most common mutations in melanoma result in hyperactivation of the mitogen-activated protein kinase (MAPK) and PI3K/AKT/ mTOR pathways responsible for initiating and controlling oncogenic protein translation. This makes both the signaling pathways potentially important therapeutic targets in melanoma. Our studies were carried out on human melanoma cell lines WM793 and 1205 LU with similar genomic alteration (BRAFV600E and PTEN loss). We used a highly specific PI3K/mTOR inhibitor, dactolisib (NVP-BEZ235), and Mnk inhibitor - CGP57380 alone and in combination. Here, we explore the mechanism of action of these drugs alone and in combination, as well as their effect on the viability and invasiveness of melanoma cells. Although when used independently, both drugs suppressed cell proliferation and migration, their combination has additional antitumor effects. We demonstrate that simultaneous inhibition of both pathways may prevent possible drug resistance. [Display omitted] • MNK and PI3K/mTOR inhibitors reduce invasiveness of melanoma cells. • Targeting of eIF4E by blocking MNK and PI3K/mTOR suppress translational machinery. • Inhibition PI3K/mTOR and Mnk activity induce autophagy and apoptosis simultaneously. • Combination of drug dactolisib and CGP57380 attenuate possible drug resistances. [ABSTRACT FROM AUTHOR]

Abstract: The role of sulfur in prostate cancer progression may be significant for understanding the process of carcinogenesis. This work, based on X-ray Absorption Near Edge Structure (XANES) spectroscopy, is focused on determination of sulfur chemical species occurring in prostate cancer cell lines. The experimental material consisted of four commercially available cell lines: three from metastasized prostate cancer (PC3, LNCaP, and DU145) and one, used as a control, from the non-tumourigenic peripheral zone of the prostate (PZ-HPV-7). The experiment was performed at the SUL-X beamline of the synchrotron radiation source ANKA, Karlsruhe (Germany). The K-edge XANES spectra of sulfur were analyzed by deconvolution in order to establish sulfur species that occur in prostate cancer cells and to find out whether there are any differences in their content between various cell lines. Experimental spectra were fitted in two ways: with two Gaussian peaks and one arctangent step function, and additionally by a Linear Combination Fit with spectra of reference compounds in order to obtain quantitative chemical information. All fitting procedures were performed with the Athena code (Ravel and Newville, 2005) and the results of deconvolution were used to determine the fraction of each sulfur form. The results of data analysis showed that cell lines from different metastasis had different ratio of reduced to oxidized sulfur species. The LCF analysis demonstrated that the highest content of GSH, one of the most important sulfur-bearing compounds in cells, was observed in DU145 cells. These findings may confirm the hypothesis of changes in redox balance in case of cancer initiation and progression. [Copyright &y& Elsevier]

• α V expression classifies bladder cancer cells into two groups. • Syndecan-4 (SDC4) expression was the largest in bladder cancer cells. • SMFS reveal various unbinding kinetics for SCD4-VN and α V β 1 –VN complexes. • Unbinding of α V β 1 from VN proceeds before the unbinding of SDC-4. The knowledge on how cells interact with microenvironment is particularly important in understanding the interaction of cancer cells with surrounding stroma, which affects cell migration, adhesion, and metastasis. The main cell surface receptors responsible for the interaction with extracellular matrix (ECM) are integrins, however, they are not the only ones. Integrins are accompanied to other molecules such as syndecans. The role of the latter has not yet been fully established. In our study, we would like to answer the question of whether integrins and syndecans, possessing similar functions, share also similar unbinding properties. By using single molecule force spectroscopy (SMFS), we conducted measurements of the unbinding properties of α V β 1 and syndecan-4 in the interaction with vitronectin (VN), which, as each ECM protein, possesses two binding sites specific to integrins and syndecans. The unbinding force and the kinetic off rate constant derived from SMFS describe the stability of single molecular complex. Obtained data show one barrier transition for each complex. The proposed model shows that the unbinding of α V β 1 from VN proceeds before the unbinding of SDC-4. However, despite different unbinding kinetics, the access to both receptors is needed for cell growth and proliferation. [ABSTRACT FROM AUTHOR]