Knockdown of TMEM45A overcomes multidrug resistance and epithelial-mesenchymal transition in human colorectal cancer cells through inhibition of TGF- β signaling pathway.

This study aimed to investigate the key role of TMEM45A in CRC by knockdown of its expression in 5-FU-resistant CRC cells (HCT-8/5-FU and SW480/5-FU) and their parental cells (HCT-8 and SW480). Data showed that TMEM45A was significantly up-regulated in HCT-8/5-FU and SW480/5-FU cells in comparison with their parental HCT-8 and SW480 cells. Knockdown of TMEM45A enhanced 5-FU sensitivity and 5-FU-induced apoptosis in HCT-8/5-FU and SW480/5-FU cells. It was also found that inhibition of TMEM45A increased the intracellular accumulation of Rhodamine-123 and down-regulated the expression of MDR1 in HCT-8/5-FU and SW480/5-FU cells. In addition, knockdown of TMEM45A suppressed migration and invasion of HCT-8/5-FU and SW480/5-FU cells. Furthermore, knockdown of TMEM45A not only attenuated MDR-enhanced epithelial-mesenchymal transition (EMT), but also suppressed MDR-enhanced activation of TGF-β signaling pathway in HCT-8/5-FU and SW480/5-FU cells. Taken together, our study suggests that knockdown of TMEM45A can effectively overcome MDR and inhibit EMT via suppression of the TGF-β signaling pathway in human CRC cells, and that targeting TMEM45A will be a potential strategy in the treatment of MDR in CRC. PMID: 31788833 [PubMed - as supplied by publisher]
Source: Clinical and Experimental Pharmacology and Physiology - Category: Drugs & Pharmacology Authors: Tags: Clin Exp Pharmacol Physiol Source Type: research

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Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
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Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
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Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
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Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
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