WT1 Enhances Proliferation and Impedes Apoptosis in KRAS Mutant NSCLC via Targeting cMyc

Wu, Chen; Wang, Sihan; Xu, C.; Tyler, Andreas; Li, Xingru; Andersson, Christian; Oji, Yusuke; Sugiyama, Haruo; Chen, Yijiang; Li, Aihong

doi:10.1159/000369726

Cited by 18 publications

(13 citation statements)

References 48 publications

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“…In NSCLC, WT1 was upregulated in cancer specimens compared with NATs (44). Functional studies revealed that WT1 enhanced cell proliferation, invasion, cisplatin-resistance and decreased apoptosis (44)(45)(46)(47). The present study, in accordance with previous findings, demonstrated that knockdown of WT1 inhibited growth, migration and invasion of NSCLC cells.…”

Section: Discussionsupporting

confidence: 91%

microRNA-361 targets Wilms' tumor 1 to inhibit the growth, migration and invasion of non-small-cell lung cancer cells

Yang

Zhang

Zhao

et al. 2016

Molecular Medicine Reports

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The expression and functions of microRNA-361 (miR-361) have been studied in various human cancers. However, its expression and role in non‑small‑cell lung cancer (NSCLC) remains unclear. In the present study, the expression levels of miR‑361 in NSCLC tissues and cell lines were determined using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). In addition, the effect of miR‑361 on the proliferation, migration and invasion of NSCLC cells was assessed. Furthermore, a dual‑Luciferase reporter assay, RT‑qPCR and western blotting were performed to investigate whether miR‑361 directly targeted the 3' untranslated region of Wilms' tumor 1 (WT1). The results of the present study revealed that miR‑361 was downregulated in NSCLC tissues and cell lines. Enforced expression of miR‑361 suppressed the proliferation, migration and invasion of NSCLC cells. WT1 was identified as a direct target gene of miR‑361 in NSCLC. Furthermore, knockdown of WT1 had similar effects to miR‑361 overexpression in NSCLC cells. The present study provided novel insights into the molecular mechanism underlying the rapid growth and metastasis of NSCLC, and identified the association between miR‑361 and WT1 as a potential therapeutic target for the treatment of NSCLC.

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Section: Discussionsupporting

confidence: 91%

microRNA-361 targets Wilms' tumor 1 to inhibit the growth, migration and invasion of non-small-cell lung cancer cells

Yang

Zhang

Zhao

et al. 2016

Molecular Medicine Reports

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“…WT1 is a gene regulator important for cell growth, apoptosis, and differentiation, and multiple genes are regulated by WT1. Interestingly, one of the WT1 targets is MYC , which is activated by WT1 but suppressed by a WT1 : BASP1 complex (Goodfellow et al , ; Green et al , ; Han et al , ; Wu et al , ). Recent studies showed that WT1 is activated in pancreatic cancer and that patients with elevated BASP1 levels have a significantly better prognosis than individuals whose cancer cells contain no BASP1 but high WT1 levels (Zhou et al , ).…”

Section: Discussionmentioning

confidence: 99%

The brain acid‐soluble protein 1 (BASP1) interferes with the oncogenic capacity of MYC and its binding to calmodulin

et al. 2020

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The MYC protein is a transcription factor with oncogenic potential controlling fundamental cellular processes such as cell proliferation, metabolism, differentiation, and apoptosis. The MYC gene is a major cancer driver, and elevated MYC protein levels are a hallmark of most human cancers. We have previously shown that the brain acid‐soluble protein 1 gene (BASP1) is specifically downregulated by the v‐myc oncogene and that ectopic BASP1 expression inhibits v‐myc‐induced cell transformation. The 11‐amino acid effector domain of the BASP1 protein interacts with the calcium sensor calmodulin (CaM) and is mainly responsible for this inhibitory function. We also reported recently that CaM interacts with all MYC variant proteins and that ectopic CaM increases the transactivation and transformation potential of the v‐Myc protein. Here, we show that the presence of excess BASP1 or of a synthetic BASP1 effector domain peptide leads to displacement of v‐Myc from CaM. The protein stability of v‐Myc is decreased in cells co‐expressing v‐Myc and BASP1, which may account for the inhibition of v‐Myc. Furthermore, suppression of v‐Myc‐triggered transcriptional activation and cell transformation is compensated by ectopic CaM, suggesting that BASP1‐mediated withdrawal of CaM from v‐Myc is a crucial event in the inhibition. In view of the tumor‐suppressive role of BASP1 which was recently also reported for human cancer, small compounds or peptides based on the BASP1 effector domain could be used in drug development strategies aimed at tumors with high MYC expression.

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“…A third major finding was no increase in CoRL proliferation in RenWt1 fl/fl mice, and enalapril had no effect. This was of interest, as several groups have shown that WT1 enhances proliferation of tumor cells and cardiac endothelial cells ( Li et al., 2015 , Wu et al., 2015 ).…”

Section: Discussionmentioning

confidence: 99%

WT1 Is Necessary for the Proliferation and Migration of Cells of Renin Lineage Following Kidney Podocyte Depletion

et al. 2017

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SummaryWilms' tumor suppressor 1 (WT1) plays an important role in cell proliferation and mesenchymal-epithelial balance in normal development and disease. Here, we show that following podocyte depletion in three experimental models, and in patients with focal segmental glomerulosclerosis (FSGS) and membranous nephropathy, WT1 increased significantly in cells of renin lineage (CoRL). In an animal model of FSGS in RenWt1fl/fl reporter mice with inducible deletion of WT1 in CoRL, CoRL proliferation and migration to the glomerulus was reduced, and glomerular disease was worse compared with wild-type mice. To become podocytes, CoRL undergo mesenchymal-to-epithelial transformation (MET), typified by reduced staining for mesenchymal markers (MYH11, SM22, αSMA) and de novo expression of epithelial markers (E-cadherin and cytokeratin18). Evidence for changes in MET markers was barely detected in RenWt1fl/fl mice. Our results show that following podocyte depletion, WT1 plays essential roles in CoRL proliferation and migration toward an adult podocyte fate.

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WT1 Enhances Proliferation and Impedes Apoptosis in KRAS Mutant NSCLC via Targeting cMyc

Cited by 18 publications

References 48 publications

microRNA-361 targets Wilms' tumor 1 to inhibit the growth, migration and invasion of non-small-cell lung cancer cells

microRNA-361 targets Wilms' tumor 1 to inhibit the growth, migration and invasion of non-small-cell lung cancer cells

The brain acid‐soluble protein 1 (BASP1) interferes with the oncogenic capacity of MYC and its binding to calmodulin

WT1 Is Necessary for the Proliferation and Migration of Cells of Renin Lineage Following Kidney Podocyte Depletion

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