Docetaxel Modulates the Delayed Rectifier Potassium Current (I K) and ATP-Sensitive Potassium Current (I KATP) in Human Breast Cancer Cells

Sun, Tao; Song, Zhiguo J.; Jiang, Daqing; Nie, Hongguang; Han, Dong-Yun

doi:10.1007/s00232-014-9757-6

Cited by 6 publications

(4 citation statements)

References 21 publications

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“…The three drugs mentioned above were reported to work by blocking the progression of the cell cycle, which ultimately led to the death of the cancer cells [ 51 , 52 ]. Paclitaxel and docetaxel might affect the proliferation of BRCA cells by modulating potassium currents, and TME could induce docetaxel resistance [ 42 , 53 , 54 ]. We concluded that KCNK1 could affect the cell cycle via potassium channels, thereby increasing drug sensitivity of BC patients to docetaxel, paclitaxel, and vincristine.…”

Section: Discussionmentioning

confidence: 99%

Overexpressed KCNK1 regulates potassium channels affecting molecular mechanisms and biological pathways in bladder cancer

Zhang,

Chen,

Wei

et al. 2024

Eur J Med Res

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Background This study aimed to explore the expression, molecular mechanism and its biological function of potassium two pore domain channel subfamily K member 1 (KCNK1) in bladder cancer (BC). Methods We integrated large numbers of external samples (n = 1486) to assess KCNK1 mRNA expression levels and collected in-house samples (n = 245) for immunohistochemistry (IHC) experiments to validate at the KCNK1 protein level. Single-cell RNA sequencing (scRNA-seq) analysis was performed to further assess KCNK1 expression and cellular communication. The transcriptional regulatory mechanisms of KCNK1 expression were explored by ChIP-seq, ATAC-seq and ChIA-PET data. Highly expressed co-expressed genes (HECEGs) of KCNK1 were used to explore potential signalling pathways. Furthermore, the immunoassay, clinical significance and molecular docking of KCNK1 were calculated. Results KCNK1 mRNA was significantly overexpressed in BC (SMD = 0.58, 95% CI [0.05; 1.11]), validated at the protein level (p < 0.0001). Upregulated KCNK1 mRNA exhibited highly distinguishing ability between BC and control samples (AUC = 0.82 [0.78–0.85]). Further, scRNA-seq analysis revealed that KCNK1 expression was predominantly clustered in BC epithelial cells and tended to increase with cellular differentiation. BC epithelial cells were involved in cellular communication mainly through the MK signalling pathway. Secondly, the KCNK1 transcription start site (TSS) showed promoter-enhancer interactions in three-dimensional space, while being transcriptionally regulated by GRHL2 and FOXA1. Most of the KCNK1 HECEGs were enriched in cell cycle–related signalling pathways. KCNK1 was mainly involved in cellular metabolism–related pathways and regulated cell membrane potassium channel activity. KCNK1 expression was associated with the level of infiltration of various immune cells. Immunotherapy and chemotherapy (docetaxel, paclitaxel and vinblastine) were more effective in BC patients in the high KCNK1 expression group. KCNK1 expression correlated with age, pathology grade and pathologic_M in BC patients. Conclusions KCNK1 was significantly overexpressed in BC. A complex and sophisticated three-dimensional spatial transcriptional regulatory network existed in the KCNK1 TSS and promoted the upregulated of KCNK1 expression. The high expression of KCNK1 might be involved in the cell cycle, cellular metabolism, and tumour microenvironment through the regulation of potassium channels, and ultimately contributed to the deterioration of BC.

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Section: Discussionmentioning

confidence: 99%

Overexpressed KCNK1 regulates potassium channels affecting molecular mechanisms and biological pathways in bladder cancer

Zhang,

Chen,

Wei

et al. 2024

Eur J Med Res

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“…The mobility and potential difference between drug‐sensitive and drug‐resistant K562 cells demonstrated that acquired resistance to different drugs resulted in changes in electrophoretic mobility and zeta potential. This difference would imply possible distinguishable electrical properties between cell types . Even though there is not any statistically significant change in electrophoretic mobility between drug‐sensitive and drug‐resistant K562 cell lines (Fig.…”

Section: Resultsmentioning

confidence: 92%

Resistance to anticancer drugs permanently alters electrophoretic mobility of cancer cell lines

2017

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Electrophoretic mobility is a physical phenomenon defining the mobility of charged particles in a solution under applied electric field. As charged biological systems, living cells including both prokaryotes and eukaryotes have been assessed in terms of electrophoretic mobility to decipher their electrochemical structure. Moreover, determination of electrophoretic mobility of living cancer cells have promoted the advance exploration of the nature of the cancer cells and separation of cancer cells from normal ones under applied electric field. However, electrophoretic mobility of drug-resistant cells has not yet been examined. In the present study, we determined the electrophoretic mobility of drug-resistant cancer cell lines for both suspension and adherent cells and compared with those of drug-sensitive counterparts. We showed that resistance to anticancer drugs alters the electrophoretic mobility in a permanent manner, even lasting without any exposure to anticancer agents for a long time period. We also studied the cellular morphologies of adherent cells where the cellular invaginations and protrusions were increased in drug-resistant adherent cells, which could be direct cause of altered surface charge and electrophoretic mobility as a result. These findings could be helpful in terms of understanding the electrophysiological and physicochemical background of drug resistance in cancer cells and developing systems to separate drug-sensitive cells from drug-resistant ones.

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“…5), and paclitaxel can activate the voltage gated Ca 2þ channel CaV3.2 (6). Docetaxel was also found to modulate the activity of K þ channels known to regulate membrane potential and therefore Ca 2þ entry (7). Interestingly, the SK3 potassium channel has been found to be associated with oxaliplatin neurotoxicity (8), and we reported a pivotal role of this channel in the regulation of Ca 2þ homeostasis and Ca 2þ -activated proteases calpains (9,10).…”

Section: Introductionmentioning

confidence: 72%

SK3 Gene Polymorphism Is Associated with Taxane Neurotoxicity and Cell Calcium Homeostasis

Rua

Guéguinou

Soubai

et al. 2018

Clinical Cancer Research

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Taxane-induced peripheral neuropathy is a common side effect induced by anticancer agents, and no drug capable of preventing its occurrence or ameliorating its long-term course has been identified. The physiology of taxane neuropathy is not clear, and diverse mechanisms have been suggested, with ion channels regulating Ca homeostasis appearing good candidates. The calcium-activated potassium channel SK3 is encoded by the gene, which is characterized by a length polymorphism due to variable number of CAG repeats. To study the influence of the polymorphism of CAG motif repeat of on the development of taxane-induced neuropathy, we evaluated 176 patients treated with taxanes for breast cancer. In parallel, we measured Ca entry using Fura2-AM dye in HEK cells expressing short versus long CAG alleles of In the current study, we report that in the presence of docetaxel, Ca entry was significantly increased in cells expressing short versus long CAG alleles of SK3 and that a SK3-lipid blocker inhibits this effect. We found that patients carrying a short allele exhibited significantly increased incidence of taxane neuropathy compared with those carrying longer alleles. The clinical implication of these findings is that polymorphism may increase patient susceptibility to taxane neurotoxicity and that the use of SK3 blockers during taxanes' administration may represent an interesting approach for the prevention of this neurotoxicity..

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Docetaxel Modulates the Delayed Rectifier Potassium Current (I K) and ATP-Sensitive Potassium Current (I KATP) in Human Breast Cancer Cells

Cited by 6 publications

References 21 publications

Overexpressed KCNK1 regulates potassium channels affecting molecular mechanisms and biological pathways in bladder cancer

Overexpressed KCNK1 regulates potassium channels affecting molecular mechanisms and biological pathways in bladder cancer

Resistance to anticancer drugs permanently alters electrophoretic mobility of cancer cell lines

SK3 Gene Polymorphism Is Associated with Taxane Neurotoxicity and Cell Calcium Homeostasis

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