TIS21/BTG2 inhibits doxorubicin-induced stress fiber-vimentin networks via Nox4-ROS-ABI2-DRF-linked signal cascade

Lim, In Kyoung; Choi, Jung A.; Kim, Eun Young; Kim, Tae Young; Jang, Soohyun; Ryu, Min Sook; Shim, Sang‐Hee

doi:10.1016/j.cellsig.2016.12.001

Cited by 8 publications

(4 citation statements)

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“…4c). We have recently reported that ABI-2 is targeted to proteasome-mediated degradation by BTG2 42 . Hence, ABI-2 was employed as a positive control of proteasome activation and confirmed that BTG2 /TIS21 expression slightly increased ubiquitination of ABI-2 protein along with its interaction (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

Translational downregulation of Twist1 expression by antiproliferative gene, B-cell translocation gene 2, in the triple negative breast cancer cells

et al. 2019

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Twist1, a key transcription factor regulating epithelial–mesenchymal transition and cancer metastasis, is highly expressed in invasive cancers in contrast to the loss of BTG2 /TIS21 expression. Based on our observation that forced expression of BTG2 /TIS21 downregulated Twist1 protein expression without altering mRNA level, we investigated molecular mechanisms of the BTG2 /TIS21 -inhibited Twist1 translation in the triple negative breast cancer (TNBC) cells and in vivo BTG2 /TIS21 -knockout (KO) mice and human breast cancer tissues. (1) C-terminal domain of Twist1 and Box B of BTG2 /TIS21 interacted with each other, which abrogated Twist1 activity. (2) BTG2 /TIS21 inhibited translational initiation by depleting eIF4E availability via inhibiting 4EBP1 phosphorylation. (3) Expression of BTG2 /TIS21 maintained p-eIF2α that downregulates initiation of protein translation, confirmed by eIF2α-AA mutant expression and BTG2 /TIS21 knockdown in MEF cells. (4) cDNA microarray analysis revealed significantly higher expression of initiation factors-eIF2A, eIF3A, and eIF4G2-in the BTG2 /TIS21 -KO mouse than that in the wild type. (5) BTG2 /TIS21 -inhibited translation initiation lead to the collapse of polysome formation and the huge peak of 80s monomer in the BTG2 /TIS21 expresser, but not in the control. (6) mRNAs and protein expressions of elongation factors were also downregulated by BTG2 /TIS21 expression in TNBC cells, but much higher in both TIS21-KO mice and lymph node-positive human breast cancers. (7) BTG2 /TIS21 -mediated Twist1 loss was not due to the protein degradation by ubiquitination and autophagy activation. (8) Twist1 protein level was significantly higher in various organs of TIS21-KO mice compared with that in the control, indicating the in vivo role of BTG2 /TIS21 gene in the regulation of Twist1 protein level. Altogether, the present study support our hypothesis that BTG2 /TIS21 is a promising target to combat with metastatic cancers with high level of Twist1 without BTG2 /TIS21 expression.

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Section: Resultsmentioning

confidence: 99%

Translational downregulation of Twist1 expression by antiproliferative gene, B-cell translocation gene 2, in the triple negative breast cancer cells

et al. 2019

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“…On the one hand, ABA can promote the synthesis of CAT and improve the efficiency of the antioxidant system. While, on the other hand, GPX1 can inhibit ABI , thereby relieving the inhibition of ABA by plants (Lim et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Identification of microRNA-target interactions for antioxidant defense response under drought stress by high-throughput sequencing in Zanthoxylum bungeanum Maxim

Fei

Hong

et al. 2019

Preprint

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12When the plant is in an unfavorable environment such as drought or high temperature, it will 13 accumulate a large amount of active oxygen, which will seriously affect the normal growth and 14 development of the plant. The antioxidant system can remove the reactive oxygen species 15 produced under drought conditions and so mitigate oxidative damage. We examined the trends of 16 antioxidant enzymes, miRNAs and their target genes in Zanthoxylum bungeanum under drought 17 stress. According to the changes of antioxidant enzymes, miRNAs and their target genes 18 expression patterns of Zanthoxylum bungeanum under drought stress, an interaction model was 19 constructed to provide a reference for further understanding of plant antioxidant mechanism. The 20 results indicate that under drought stress, POD, CAT, APX, proline, MDA and related genes all 21show positive responses to drought, while SOD and its genes showed a negative response. It is 22 23 play a major role, and SOD plays a supporting role. In addition, the expression levels of miRANs 24 and their target genes were basically negatively correlated, indicating that miRNAs are involved 25 in the regulation of the antioxidant system of Zanthoxylum bungeanum. 26 Keywords：antioxidant system; Zanthoxylum bungeanum Maxim.; reactive oxygen species; 27 drought stress；miRNA-Target gene 28 29 42 Drought stress can cause a series of physiological and molecular reactions in plants, which 43 seriously affect normal growth. Thus, drought can cause imbalances in cellular reactive oxygen 44 3 species (ROS), it can also upset cell membrane lipid peroxidation and it can damage cell and 45 organelle membranes. Excessive ROS have toxic effects on plants. Irrigated agriculture is not yet 46 general, so drought remains one of the most important unfavorable factors affecting both the 47

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“…CRISPR screening uncovered that ABI2 is a key determinant of multiple drug resistance in pancreatic cancer cells 17 . Kyoung Lim's research demonstrated that the Doxo‐induced HCC cell senescence can be attenuated by TIS21 through inhibiting linear actin nucleation, which is regulated by Nox4‐ROS‐ABI2‐DRF signal cascade 18 . These studies indicated that ABI2 might play a crucial role in drug resistance and relapse of tumour.…”

Section: Introductionmentioning

confidence: 99%

“… 17 Kyoung Lim's research demonstrated that the Doxo‐induced HCC cell senescence can be attenuated by TIS21 through inhibiting linear actin nucleation, which is regulated by Nox4‐ROS‐ABI2‐DRF signal cascade. 18 These studies indicated that ABI2 might play a crucial role in drug resistance and relapse of tumour. However, the potential functions and underlying mechanisms of ABI2 in malignant tumours, especially HCC, are largely unclear.…”

Section: Introductionmentioning

confidence: 99%

ABI2‐mediated MEOX2/KLF4‐NANOG axis promotes liver cancer stem cell and drives tumour recurrence

Chen

Zhang

et al. 2022

Liver International

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Tumour recurrence and drug resistance in hepatocellular carcinoma remain challenging.Cancer stem cells (CSCs) are responsible for tumour initiation because of their stemness characteristics. CSCs accounting for drug resistance and tumour relapse are promising therapeutic targets. We report that Abelson interactor 2 (ABI2) is a novel therapeutic target of HCC CSCs. First, ABI2 was upregulated in HCC tissues compared with liver tissues and was associated with tumour size, pathological grade, liver cirrhosis, worse prognosis and a high recurrence rate. Functional studies illustrate that ABI2 knockdown suppresses cell growth, migration, invasion and sorafenib resistance in vitro. Furthermore, ABI2 knockdown inhibited HCC sphere formation and decreased the CD24 + , CD133 + and CD326 + CSCs populations, suggesting the suppression of HCC stemness characteristics.A tumour xenograft model and limiting dilution assay demonstrated the inhibition of tumorigenicity and tumour initiation. Moreover, molecular mechanism studies showed that ABI2 recruits and directly interacts with the transcription factor MEOX2, which binds to the KLF4 and NANOG promoter regions to activate their transcription. Furthermore, overexpression of MEOX2 restored HCC malignant behaviour and the CSC population.The ABI2-mediated transcriptional axis MEOX2/KLF4-NANOG promotes HCC growth, metastasis and sorafenib resistance by maintaining the CSC population, suggesting that ABI2 is a promising CSC target in HCC treatment.

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TIS21/BTG2 inhibits doxorubicin-induced stress fiber-vimentin networks via Nox4-ROS-ABI2-DRF-linked signal cascade

Cited by 8 publications

References 54 publications

Translational downregulation of Twist1 expression by antiproliferative gene, B-cell translocation gene 2, in the triple negative breast cancer cells

Translational downregulation of Twist1 expression by antiproliferative gene, B-cell translocation gene 2, in the triple negative breast cancer cells

Identification of microRNA-target interactions for antioxidant defense response under drought stress by high-throughput sequencing in Zanthoxylum bungeanum Maxim

ABI2‐mediated MEOX2/KLF4‐NANOG axis promotes liver cancer stem cell and drives tumour recurrence

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