AF1q is a novel TCF7 co-factor which activates CD44 and promotes breast cancer metastasis

Park, Jino; Schlederer, Michaela; Schreiber, Martin; Ice, Ryan J.; Merkel, Olaf; Bilban, Martin; Hofbauer, Sebastian L.; Kim, Soojin; Addison, Joseph; Zou, Jie; Ji, Chunyan; Bunting, Silvia T.; Wang, Zhengqi; Shoham, Menachem; Huang, Gang; Bagó-Horváth, Zsuzsanna; Gibson, Laura F.; Rojanasakul, Yon; Remick, Scot C.; Ivanov, Alexey V.; Pugacheva, Elena N.; Bunting, Kevin D.; Moriggl, Richard; Kenner, Lukas; Tse, William

doi:10.18632/oncotarget.4136

Cited by 40 publications

(70 citation statements)

References 45 publications

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“…It was reported that AF1q enhanced Wnt signaling pathway by interacting with TCF7 to activate CD44 transcription [15]. We further confirmed the interactions between AF1q and TCF7.…”

Section: Resultssupporting

confidence: 85%

“…However, this effect may be indirect because we found that AF1q specifically binds to TCF7. It was demonstrated that AF1q promotes transcriptional rates through increasing the formation of transcriptional complex with lymphoid enhancer-binding factor (LEF) and β-catenin [15]. Additionally, we found that TCF7 transcriptional level was also increased by AF1q.…”

Section: Discussionmentioning

confidence: 54%

“…Recently, Park J et al . reported AF1q promotes metastasis of breast cancer via specifically binding to TCF7 in the Wnt signaling [15]. Based on the important role of Wnt in kidney, we investigated whether AF1q regulates Wnt signaling.…”

Section: Discussionmentioning

confidence: 99%

“…Although no studies have investigated the roles of AF1q in kidney, it was recently reported that AF1q could stimulate Wnt signaling by directly binding to T-cell-factor-7 (TCF7) [15]. In present study, we aimed to investigate whether AF1q participates in the pathogenesis of podocytes injury and its underlying mechanism.…”

Section: Introductionmentioning

confidence: 97%

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AF1q Contributes to Adriamycin-Induced Podocyte Injury by Activating Wnt/β-Catenin Signaling

Ren

Sun

et al. 2017

Kidney Blood Press Res

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Background/Aims: Injury of podocytes plays an important role in decline of glomerular filtration and proteinuria. It is well-known that proteinuria is associated with numerous chronic kidney diseases (CKD). However, the underlying mechanism of podocyte injury remains unclear. Methods: We used reverse transcription-quantitative PCR (RT-qPCR) to compare the expression level of the ALL1-fused from the chromosome 1q (AF1q) gene in mice and mouse podocytes (MPC5) with or without Adriamycin (ADR) treatment. The effects of AF1q on Wnt/ β-catenin signaling were investigated by determining the expressions of desmin, snail, WT1, nephrin and E-cadherin using western blotting. Results: We found that AF1q expression was elevated in podocytes treated with ADR than untreated cells. AF1q overexpression directly led to podocytes injury with increased levels of desmin and snail. Luciferase activity of TOPflash reporter was significantly increased in cells with AF1q overexpression than wild type cells whereas deletion of T-cell-factor-7 (TCF7) eliminated this effect. Immunoprecipitation assay evidenced that AF1q interacted with TCF7 and promoted both transcriptional and translational expressions of TCF7. Overexpression of AF1q increased protein expression of β-catenin. However, in podocytes with deletion of TCF7, AF1q was not able to promote β-catenin expression. Conclusion: Our findings demonstrated that aberrant expression of AF1q may activate Wnt/β-catenin signaling and result in podocyte injury.

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“…It was reported that AF1q enhanced Wnt signaling pathway by interacting with TCF7 to activate CD44 transcription [15]. We further confirmed the interactions between AF1q and TCF7.…”

Section: Resultssupporting

confidence: 85%

Section: Discussionmentioning

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

See 2 more Smart Citations

AF1q Contributes to Adriamycin-Induced Podocyte Injury by Activating Wnt/β-Catenin Signaling

Ren

Sun

et al. 2017

Kidney Blood Press Res

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“…The consensus today is that AF1q plays an important role in malignancy of solid tumors, but the molecular mechanisms by which AF1q interacts with oncoproteins or influences tumor suppressor gene loss are incompletely understood. We previously demonstrated that AF1q physically interacts with the HMG box protein TCF7, a key factor in Wnt signaling, and AF1q enhances expression of Wnt target genes [26]. The AF1q-TCF7 interaction results in enhanced expression of CD44, a ubiquitous multi-structural and multi-functional cell surface glycoprotein involved in adhesion, migration, and homing of cells.…”

Section: Introductionmentioning

confidence: 99%

MLLT11/AF1q boosts oncogenic STAT3 activity through Src-PDGFR tyrosine kinase signaling

et al. 2016

Self Cite

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Constitutive STAT3 activation by tyrosine phosphorylation of mutated or amplified tyrosine kinases (pYSTAT3) is critical for cancer initiation, progression, invasion, and motility of carcinoma cells. We showed that AF1q is associated with STAT3 signaling in breast cancer cells. In xenograft models, enhanced AF1q expression activated STAT3 and promoted tumor growth and metastasis in immunodeficient NSG mice. The cytokine secretory phenotype of MDA-MB-231LN breast cancer cells with altered AF1q expression revealed changes in expression of platelet-derived growth factor subunit B (PDGF-B). AF1q-induced PDGF-B stimulated motility, migration, and invasion of MDA-MB-231LN cells, and AF1q up-regulated platelet-derived growth factor receptor (PDGFR) signaling. Further, AF1q-induced PDGFR signaling enhanced STAT3 activity through Src kinase activation, which could be blocked by the Src kinase inhibitor PP1. Moreover, AF1q up-regulated tyrosine kinase signaling through PDGFR signaling, which was blockable by imatinib. In conclusion, we demonstrated that enhanced AF1q expression contributes to persistent and oncogenic pYSTAT3 levels in invasive carcinoma cells by activating Src kinase through activation of the PDGF-B/PDGFR cascade. Therefore, AF1q plays an essential role as a cofactor in PDGF-B-driven STAT3 signaling.

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Cerebellar granule cell migration and folia development require Mllt11/Af1q/Tcf7c

Blommers,

Stanton‐Turcotte,

Witt

et al. 2024

Developmental Neurobiology

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The organization of neurons into distinct layers, known as lamination, is a common feature of the nervous system. This process, which arises from the direct coupling of neurogenesis and neuronal migration, plays a crucial role in the development of the cerebellum, a structure exhibiting a distinct folding cytoarchitecture with cells arranged in discrete layers. Disruptions to neuronal migration can lead to various neurodevelopmental disorders, highlighting the significance of understanding the molecular regulation of lamination. We report a role Mllt11/Af1q/Tcf7c (myeloid/lymphoid or mixed‐lineage leukemia; translocated to chromosome 11/All1 fused gene from chromosome 1q, also known as Mllt11 transcriptional cofactor 7; henceforth referred to Mllt11) in the migration of cerebellar granule cells (GCs). We now show that Mllt11 plays a role in both the tangential and radial migration of GCs. Loss of Mllt11 led to an accumulation of GC precursors in the rhombic lip region and a reduction in the number of GCs successfully populating developing folia. Consequently, this results in smaller folia and an overall reduction in cerebellar size. Furthermore, analysis of the anchoring centers reveals disruptions in the perinatal folia cytoarchitecture, including alterations in the Bergmann glia fiber orientation and reduced infolding of the Purkinje cell plate. Lastly, we demonstrate that Mllt11 interacts with non‐muscle myosin IIB (NMIIB) and Mllt11 loss–reduced NMIIB expression. We propose that the dysregulation of NMIIB underlies altered GC migratory behavior. Taken together, the findings reported herein demonstrate a role for Mllt11 in regulating neuronal migration within the developing cerebellum, which is necessary for its proper neuroanatomical organization.

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AF1q is a novel TCF7 co-factor which activates CD44 and promotes breast cancer metastasis

Cited by 40 publications

References 45 publications

AF1q Contributes to Adriamycin-Induced Podocyte Injury by Activating Wnt/β-Catenin Signaling

AF1q Contributes to Adriamycin-Induced Podocyte Injury by Activating Wnt/β-Catenin Signaling

MLLT11/AF1q boosts oncogenic STAT3 activity through Src-PDGFR tyrosine kinase signaling

Cerebellar granule cell migration and folia development require Mllt11/Af1q/Tcf7c

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