Cancer Drug-Resistance and a Look at Specific Proteins: Rho GDP-Dissociation Inhibitor 2, Y-Box Binding Protein 1, and HSP70/90 Organizing Protein in Proteomics Clinical Application

Abstract

Resistance to anti-cancer drugs is a well recognized problem and very often it is responsible for failure of the cancer treatment. In this study, the proteome alterations associated with the development of acquired resistance to cyclin-depedent kinases inhibitor bohemine, a promising anti-cancer drug, were analyzed with the primary aim of identifying potential targets of resistance within the cell that could pave a way to selective elimination of specific resistant cell types. A model of parental susceptible CEM T-lymphoblastic leukemia cells and its resistant counterpart CEM-BOH was used and advanced 2-D liquid chromatography was applied to fractionate cellular proteins. Differentially expressed identified proteins were further verified using immunoblotting and immunohistochemistry. Our study has revealed that Rho GDP-dissociation inhibitor 2, Y-box binding protein 1, and the HSP70/90 organizing protein have a critical role to play in resistance to cyclin-depedent kinases inhibitor. The results indicated not only that quantitative protein changes play an important role in drug-resistance, but also that there are various other parameters such as truncation, post-translational modification(s), and subcellular localization of selected proteins. Furthermore, these proteins were validated for their roles in drug resistance using different cell lines resistant to diverse representatives of anti-cancer drugs such as vincristine and daunorubicin.

Regulation of Vascular Endothelial Cell Polarization and Migration by Hsp70/Hsp90-Organizing Protein

“…In addition, the anti-angiogenesis strategy has been employed in cancer treatment [19]–[21]. Given the critical role of HOP in angiogenesis [51], it will be interesting to investigate in the future the potential of HOP as an anti-cancer drug target.…”

Cancer Cell Response to Anthracyclines Effects: Mysteries of the Hidden Proteins Associated with These Drugs

“…Additionally, involvement of multifunctional protein PPIA in cancer progression has been described [23]. Interestingly, several cytoskeleton regulating proteins including CFL1 [24] and EZR [25] were associated with invasion and metastasis and ARHGDIB was linked to the development of chemoresistance [26]. These proteins, although non-specific as regards used drugs and functioning in various biological processes, most probably present important targets underlying anti-cancer mechanisms and possibly play role of anchor molecules which may connect different pathways in a very complex regulation of cancer cell processes.…”

Rho GTPases: Anti- or pro-neoplastic targets?

“…150 Overexpression of RhoGDI1 increased resistance of cancer cells to the induction of apoptosis by chemotherapeutic agents etoposide and doxorubicin, 151 and RhoGDI2 was identified as a key player in resistance to a cyclin-dependent kinases inhibitor. 152 Thus, combined inhibition of Rho signaling with other anti-cancer therapy may be useful to achieve greater efficacy while reducing potential resistance. To this end, ROCK inhibitor fasudil and MEK inhibitor trametinib cooperatively induced apoptosis in N-Ras mutant melanoma.…”