Myeloid cell leukemia-1 promotes epithelial-mesenchymal transition of human gastric cancer cells

Abstract

Epithelial-mesenchymal transition (EMT) is a critical process that occurs during cancer progression, and cancer stem cells have been shown to acquire the EMT phenotype. Myeloid cell leukemia-1 (Mcl-1) has been implicated in cancer progression and is overexpressed in a variety of human cancers. However, the interaction between Mcl-1 and EMT in human gastric cancer (GC) is unclear. We investigated the impact of Mcl-1 expression levels on EMT and the underlying signaling pathways in human GC cells. We used the human GC cell lines, AGS and SNU638, and small interfering RNAs (siRNAs) to evaluate the effects of Mcl-1 knockdown on cell adhesion, migration and invasion. Expression of Mcl-1 and other target genes was determined using reverse transcription-polymerase chain reaction assays and western blotting. The results revealed that expression levels of Mcl-1 mRNA and protein in the AGS and SNU638 cells were reduced following transfection with Mcl-1 siRNAs. Knockdown of Mcl-1 led to increased cellular adhesion to fibronectin and collagen. Expression levels of vimentin, MMP-2, MMP-9 and Snail protein were decreased following knockdown of Mcl-1. However, expression of E-cadherin was increased in the AGS cells following knockdown of Mcl-1. The expression of cancer stemness markers, such as CD44 and CD133, was not altered by knockdown of Mcl-1. Knockdown of Mcl-1 suppressed tumor cell migration and invasion in both human GC cell lines. Signaling cascades, including the β-catenin, MEK1/2, ERK1/2 and p38 pathways, were significantly blocked by knockdown of Mcl-1. Our results indicate that Mcl-1 expression induces EMT via β-catenin, MEK1/2 and MAPK signaling pathways, which subsequently stimulates the invasive and migratory capacity of human GC cells.

Selective targeting of antiapoptotic BCL‐2 proteins in cancer

“…Due to short half‐life and the possibility of having different post‐translational modifications, MCL‐1 has also been proposed to be a molecular timer for integration of different signaling outputs . Other than these attained roles of MCL‐1, this antiapoptotic BCL‐2 family member was shown to be involved in cell proliferation, autophagy, necroptosis, and epithelial–mesenchymal transition . Overall, each of these biological mechanisms should be investigated when inhibiting MCL‐1 so that inhibition toward MCL1‐1 is maintained without any undesirable outcomes.…”

Retracted: MicroRNA‐105 promotes epithelial‐mesenchymal transition of nonsmall lung cancer cells through upregulating Mcl‐1

“…14 The expression of Mcl-1 has been shown to contribute to the metastatic capacity of tumor cells through promotion of EMT. 15 In this study, the regulation between miR-105 and Mcl-1 was studied to test Figure 4A show that the messenger RNA and protein levels of Mcl-1 were both upregulated in the miR-105 mimic group, while they were downregulated in the miR-105 inhibitor group, indicating Mcl-1 was positively regulated by miR-105. Next, the expression levels of Mcl-1 in A549 and Calu-3 cells were overexpressed and suppressed by transfection, and the changes in cell viability, migration, and EMT process were reassessed.…”

Contribution of GPD2/mGPDH to an alternative respiratory chain of the mitochondrial energy metabolism and the stemness in CD133‐positive HuH‐7 cells

“…As for p38, it has been reported that p38 activity and the expression of CD133 may have correlation in cancer stem cells originating from lung cancer, melanoma and liver cancer (Erdogan et al, ; Kumar et al, ; Wang et al, ; Yang et al, ; Zhao, Jia, Han, & Zhang, ). Furthermore, it has been shown that inhibition of p38 kinase activity suppressed cancer stem cell characteristics such as migration, infiltration and anchorage‐independent growth (Lee et al, ). However, enhanced activation of p38 in cancer stem cells of colon cancer, rhabdomyosarcoma and melanoma was found to stimulate cell death (Boothello et al, ; Ciccarelli et al, ; El‐Khattouti et al, ).…”

“…of p38 kinase activity suppressed cancer stem cell characteristics such as migration, infiltration and anchorage-independent growth (Lee et al, 2015). However, enhanced activation of p38 in cancer stem cells of colon cancer, rhabdomyosarcoma and melanoma was found to stimulate cell death (Boothello et al, 2019;Ciccarelli et al, 2016;El-Khattouti et al, 2015).…”