The lost intrinsic fragmentation of MAT1 protein during granulopoiesis promotes the growth and metastasis of leukemic myeloblasts

Lou, Siyue; Liu, Gang; Shimada, Hiroyuki; Yang, Xiaochun; He, Qiaojun; Wu, Liquan

doi:10.1002/stem.1444

Cited by 12 publications

(16 citation statements)

References 48 publications

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“…The resistance factor in HepG2, Bel-7402 and SMMC-7721 cells were 14.58 ± 2.42, 12.57 ± 2.36, 10.93 ± 2.92, respectively (Figure 1A ). Additionally, BrdU proliferation [ 38 ] and trypan blue exclusion assays [ 39 ] were introduced to further display the hypoxia resistance. As shown in Figure 1B (right panel), a significant reduction of proliferation inhibition, determined by BrdU colorimetric assay, was observed in hypoxic SN38-treated groups.…”

Section: Resultsmentioning

confidence: 99%

Nuclear translocation and activation of YAP by hypoxia contributes to the chemoresistance of SN38 in hepatocellular carcinoma cells

et al. 2016

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Although hypoxia is a prominent feature contributing to the therapeutic resistance of hepatocellular carcinoma cells (HCC) against chemotherapeutic agents, including the Topoisomerase I inhibitor SN38, the underlying mechanism is not fully understood and its understanding remains a major clinical challenge. In the present study, we found that hypoxia-induced nuclear translocation and accumulation of YAP acted as a survival input to promote resistance to SN38 in HCC. The induction of YAP by hypoxia was not mediated by HIF-1α because manipulating the abundance of HIF-1α with CoCl2, exogenous expression, and RNA interference had no effect on the phosphorylation or total levels of YAP. The mevalonate-HMG-CoA reductase (HMGCR) pathway may modulate the YAP activation under hypoxia. Combined YAP inhibition using either siRNA or the HMGCR inhibitor statins together with SN38 treatment produced improved anti-cancer effects in HCC cells. The increased anti-cancer effect of the combined treatment with statins and irinotecan (the prodrug of SN-38) was further validated in a human HepG2 xenograft model of HCC in nude mice. Taken together, our findings identify YAP as a novel mediator of hypoxic-resistance to SN38. These results suggest that the administration of SN28 together with the suppression of YAP using statins is a promising strategy for enhancing the treatment response in HCC patients, particularly in advanced stage HCC cases presenting hypoxic resistance.

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Section: Resultsmentioning

confidence: 99%

Nuclear translocation and activation of YAP by hypoxia contributes to the chemoresistance of SN38 in hepatocellular carcinoma cells

et al. 2016

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“…The CDK‐activating kinase assembly factor MAT1 (MNAT1) was found in our previous study to be significantly downregulated by Difference Gel Electrophoresis (DIGE) and mass spectrometry in ADRM1 RNAi‐treated ovarian cancer cells compared to untreated parental and nontargeting siRNA‐treated cells (Fejzo et al, ). MNAT1 has recently been shown to be involved in migration and metastasis in other cancer types (Lou et al, ; Wang et al, ). The hepatocyte growth factor‐regulated tyrosine kinase substrate (HRS) was also found in our previous study to be significantly downregulated by DIGE and mass spectrometry in ADRM1 RNAi‐treated ovarian cancer cells compared to untreated parental and nontargeting siRNA‐treated cells (Fejzo et al, ).…”

Section: Resultsmentioning

confidence: 99%

ADRM1‐amplified metastasis gene in gastric cancer

Fejzo

Anderson

Chen

et al. 2015

Genes Chromosomes & Cancer

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The proteasome ubiquitin receptor ADRM1 has been shown to be a driver for 20q13.3 amplification in epithelial cancers including ovarian and colon cancer. We performed array-CGH on 16 gastric cancer cell lines and found 20q13.3 to be amplified in 19% with the minimal amplified region in gastric cancer cell line AGS spanning a 1 Mb region including ADRM1. Expression microarray analysis shows overexpression of only two genes in the minimal region, ADRM1 and OSBPL2. While RNAi knockdown of both ADRM1 and OSBPL2 led to a slight reduction in growth, only ADRM1 RNAi knockdown led to a significant reduction in migration and growth in soft-agar. Treatment of AGS cells with the ADRM1 inhibitor RA190 resulted in proteasome inhibition, but RNAi knockdown of ADRM1 did not. However, RNAi knockdown of ADRM1 led to a significant reduction in specific proteins including MNAT1, HRS, and EGFR. We hypothesize that ADRM1 may act in ADRM1-amplified gastric cancer to alter protein levels of specific oncogenes resulting in an increase in metastatic potential. Selective inhibition of ADRM1 independent of proteasome inhibition may result in a targeted therapy for ADRM1-amplified gastric cancer. In vivo models are now warranted to validate these findings. © 2015 Wiley Periodicals, Inc.

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“…Next, AML HL60R cells, harboring a RARαΔAF-2 domain and exhibiting relative resistance to RA, were used to determine the differentiation induction effect of ATRA and TAK165 18 . As illustrated in Fig.…”

Section: Resultsmentioning

confidence: 99%

The HER2 inhibitor TAK165 Sensitizes Human Acute Myeloid Leukemia Cells to Retinoic Acid-Induced Myeloid Differentiation by activating MEK/ERK mediated RARα/STAT1 axis

Shao

Liu

et al. 2016

Sci Rep

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The success of all-trans retinoic acid (ATRA) in differentiation therapy for patients with acute promyelocytic leukemia (APL) highly encourages researches to apply this therapy to other types of acute myeloid leukemia (AML). However, AML, with the exception of APL, fails to respond to differentiation therapy. Therefore, research strategies to further sensitize cells to retinoids and to extend the range of AMLs that respond to retinoids beyond APLs are urgently needed. In this study, we showed that TAK165, a HER2 inhibitor, exhibited a strong synergy with ATRA to promote AML cell differentiation. We observed that TAK165 sensitized the AML cells to ATRA-induced cell growth inhibition, G0/G1 phase arrest, CD11b expression, mature morphologic changes, NBT reduction and myeloid regulator expression. Unexpectedly, HER2 pathway might not be essential for TAK165-enhanced differentiation when combined with ATRA, while the enhanced differentiation was dependent on the activation of the RARα/STAT1 axis. Furthermore, the MEK/ERK cascade regulated the activation of STAT1. Taken together, our study is the first to evaluate the synergy of TAK165 and ATRA in AML cell differentiation and to assess new opportunities for the combination of TAK165 and ATRA as a promising approach for future differentiation therapy.

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The lost intrinsic fragmentation of MAT1 protein during granulopoiesis promotes the growth and metastasis of leukemic myeloblasts

Cited by 12 publications

References 48 publications

Nuclear translocation and activation of YAP by hypoxia contributes to the chemoresistance of SN38 in hepatocellular carcinoma cells

Nuclear translocation and activation of YAP by hypoxia contributes to the chemoresistance of SN38 in hepatocellular carcinoma cells

ADRM1‐amplified metastasis gene in gastric cancer

The HER2 inhibitor TAK165 Sensitizes Human Acute Myeloid Leukemia Cells to Retinoic Acid-Induced Myeloid Differentiation by activating MEK/ERK mediated RARα/STAT1 axis

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