Kinesins are a superfamily of motor proteins and often deregulated in different cancers. However, the mechanism of their deregulation has been poorly understood. Through examining kinesin gene family expression in estrogen receptor (ER)-positive breast cancer cells, we found that estrogen stimulation of cancer cell proliferation involves a concerted regulation of specific kinesins. Estrogen strongly induces expression of 19 kinesin genes such as Kif4A/4B, Kif5A/5B, Kif10, Kif11, Kif15, Kif18A/18B, Kif20A/20B, Kif21, Kif23, Kif24, Kif25 and KifC1 while suppresses the expression of 7 others including Kif1A, Kif1C, Kif7 and KifC3. Interestingly, the bromodomain protein ANCCA/ATAD2, previously shown to be an estrogen-induced chromatin regulator, plays a crucial role in the up- and down-regulation of kinesins by estrogen. Its overexpression drives estrogen-independent up-regulation of specific kinesins. Mechanistically, ANCCA mediates E2-dependent recruitment of E2F and MLL1 histone methyltransferase at kinesin gene promoters for gene activation associated H3K4me3 methylation. Importantly, elevated levels of Kif4A, Kif15, Kif20A and Kif23 correlate with that of ANCCA in the tumors and with poor relapse-free survival of ER-positive breast cancer patients. Their knockdown strongly impeded proliferation and induced apoptosis of both tamoxifen-sensitive and -resistant cancer cells. Together, the study reveals ANCCA as a key mediator of kinesin family deregulation in breast cancer and the crucial role of multiple kinesins in growth and survival of the tumor cells. Implications These findings support the development of novel inhibitors of cancer-associated kinesins and their regulator ANCCA for effective treatment of cancers including tamoxifen-resistant breast cancers.

The ion interaction approach developed by Pitzer allows the prediction of thermodynamic characteristics of mixed electrolyte solutions at various temperatures, if the respective parameters for each type of single electrolyte solution are known. Among such thermodynamic characteristics are the volumetric ones (density and apparent molal volumes). A database for the densities and the apparent molal volumes versus concentrations was developed at a temperature interval of 288.15–368.15 K using all available literature sources for each single electrolyte solution formed by various electrically neutral combinations of the following ions (Na+, K+, Mg2+, Ca2+, Sr2+, Ba2+, Cl−, Br−, HCO3−, CO32−, and SO42−). These are the most important ions for industrial solutions as well as for natural waters. Statistical treatment was applied to this database in order to discard poor data. The proper treatment of all sound quality apparent molal volumes, in a wide range of concentrations from infinite dilution through saturation, allowed us to compute sets of volumetric ion interaction parameters (V̄MX0, βMX(0)V, βMX(1)V, βMX(2)V, and CMXV) at various temperatures in a 288.15–368.15 K temperature interval. The validity of the selected sets at various temperatures was demonstrated by a comparison of the experimental and calculated densities for multiple-solute electrolyte solutions containing NaCl, KCl, MgCl2, and CaCl2 with an ionic strength reaching 9.23 that resembled Dead Sea water.

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