KIF23 promotes autophagy‐induced imatinib resistance in chronic myeloid leukaemia through activating Wnt/β‐catenin pathway. (29th September 2022)

• Record Type: Journal Article
• Authors: Huang, Yong; Yuan, Chunyan; Liu, Qiwei; Wang, Lingying
• Is Part Of: Clinical and experimental pharmacology and physiology. Volume 49:Number 12(2022)
• Page Start: 1334
• Page End: 1341
• Publication Date: 2022-09-29
• Subjects: autophagy -- chronic myeloid leukaemia -- imatinib resistance -- KIF23 -- Wnt/β‐catenin; Clinical pharmacology -- Periodicals; Pharmacology, Experimental -- Periodicals; Physiology, Experimental -- Periodicals; Physiology, Pathological -- Periodicals; 615.1
• DOI: 10.1111/1440-1681.13718
• Languages: English
• ISSNs: 0305-1870

Abstract

Abstract: Imatinib, an inhibitor of tyrosine kinase, shows remarkable efficacy in chronic myeloid leukaemia (CML). Autophagy protects tumour cells against chemotherapeutic stimulation and contributes to imatinib resistance in CML. Kinesin family member 23 (KIF23) is involved in cytokinesis and associated with autophagy. The role of KIF23 in autophagy‐induced imatinib resistance in CML was investigated. First, to induce drug resistance, CML cells were exposed to increasing concentrations of imatinib. The concentration of imatinib resistance in CML cells was screened through upregulation of 50% inhibitory concentration (IC50 ) values. KIF23 was elevated in imatinib‐resistant tissues and cells of CML. Second, knockdown of KIF23 reduced IC50 values of imatinib‐resistant CML cells to imatinib. Moreover, silence of KIF23 also suppressed cell proliferation and promoted apoptosis of imatinib‐resistant CML cells. Third, immunofluorescence analysis showed that the number of LC3 bright spots in imatinib‐resistant CML cells was reduced by silence of KIF23. Knockdown of KIF23 upregulated p62 expression and downregulated the expression ratio of LC3‐II to LC3‐I in imatinib‐resistant CML cells. Last, silence of KIF23 decreased nuclear β‐catenin and increased cytoplasmic β‐catenin in imatinib‐resistant CML cells. Activator of Wnt/β‐catenin attenuated KIF23 silence‐induced increase of apoptosis and decrease of autophagy in imatinib‐resistant CML cells. In conclusion, loss of KIF23 repressed autophagy‐induced imatinib resistance in CML cells through inactivation of Wnt/β‐catenin pathway.