PKB/Akt kinase localization and role in stemness maintenance in cancer

Sammanfattning: Cancer incidence rates have increased over the last decade. Currently available therapies are only moderately effective in targeting cancer cells. Established cancer treatment protocols fail to eliminate populations of cancer stem cells (CSCs), which develop resistance against the chemotherapeutic drugs and lead to cancer recurrence. Therefore, understanding the mechanisms by which CSCs resist drugs and identifying molecular markers are both necessary to further improve prognosis and to develop new treatment strategies. Increased protein kinase B/Akt1 gene expression and/or activity have been found increased in majority of cancer types. Akt1 is a key player in PI3K-AktmTOR pathway that is vital for cell survival, proliferation, migration, invasion, metastasis, angiogenesis and apoptosis. In this study, we investigated a series of novel markers to improve the characterization of CSCs, with particular focus the roles of Akt in CSC maintenance and the regulatory role of micro-RNA (miR) in cancer cells. While utilizing in breast cancer cells as models, we found that luminescent conjugated oligothiophenes (LCOs), p-HTMI and p-HTAA have the potential to differentially stain various subpopulations of cancer cells, presumably also CSCs among breast cancer cells. However, further studies are needed to confirm these results. Additionally, when we investigated the effect of Akt intracellular compartmentalization on CSC development, the results revealed that nuclear Akt enhances CSC proliferation (ALDH +/High CD44+/High/CD24-/Low) and clonogenicity, which was counter examined and confirmed by using the Aktspecific inibitor triciribine. Furthermore, while investigating the impact of Akt on miR regulation in cancer cells, we found that Akt overexpression decreased.