Hepatocyte Growth Factor (Hgf) Stimulates Low Density Lipoprotein Receptor-related Protein (Lrp) 5/6 Phosphorylation and Promotes Canonical Wnt Signaling

Koraishy, Farrukh M.; Silva, Cynthia; Mason, Sherene; Wu, Dianqing; Cantley, Lloyd G.

doi:10.1074/jbc.m114.563213

Cited by 23 publications

(19 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, HGF has been shown to stimulate β-catenin by inducing its tyrosine phosphorylation and translocation into the nucleus, or inducing LRP-5/6 phosphorylation, via a Wnt-independent pathway. 100 , 101 Since HGF, its c-met receptor and β-catenin are markedly activated after AKI, 99 these suggest that HGF and Wnt signaling may work in concert to promote tubular cell proliferation. 102 , 103 In addition, other developmental signaling such as Shh and Notch may crosstalk with Wnt in promoting tissue repair after injury.…”

Section: Wnt/β-catenin and Adaptive Repair After Akimentioning

confidence: 99%

Wnt/β-catenin signaling in kidney injury and repair: a double-edged sword

Zhou

Tan

et al. 2016

Laboratory Investigation

161

133

View full text Add to dashboard Cite

The Wnt/β-catenin signaling cascade is an evolutionarily conserved, highly complex pathway that is known to be involved in kidney injury and repair after a wide variety of insults. While the kidney displays an impressive ability to repair and recover after injury, these repair mechanisms can be overwhelmed, leading to maladaptive responses and eventual development of chronic kidney disease (CKD). Emerging evidence demonstrates that Wnt/β-catenin signaling possesses dual roles in promoting repair/regeneration or facilitating progression to CKD after acute kidney injury (AKI), depending on the magnitude and duration of its activation. In this review, we summarize the expression, intracellular modification, and secretion of Wnt family proteins and their regulation in a variety of kidney diseases. We also explore our current understanding of the potential mechanisms by which transient Wnt/β-catenin activation positively regulates adaptive responses of the kidney after AKI, and discuss how sustained activation of this signaling triggers maladaptive responses and causes destructive outcomes. A better understanding of these mechanisms may offer important opportunities for designing targeted therapy to promote adaptive kidney repair/recovery and prevent progression to CKD in patients.

show abstract

Section: Wnt/β-catenin and Adaptive Repair After Akimentioning

confidence: 99%

Wnt/β-catenin signaling in kidney injury and repair: a double-edged sword

Zhou

Tan

et al. 2016

Laboratory Investigation

161

133

View full text Add to dashboard Cite

show abstract

“…Some extracellular cues do not bind to LRP6, per se , but regulate the activity of kinases used to phosphorylate LRP6, thereby activating β-catenin signaling. For example, hepatocyte growth factor (HGF) can stimulate GSK3-dependent and Wnt-independent LRP6 phosphorylation, thereby stabilizing β-catenin and activating Wnt signaling ( Koraishy et al, 2014 ). In addition, fibroblast growth factor 2 (FGF2) promotes the phosphorylation of LRP6 and accumulation of β-catenin in an ERK1/2-dependent manner ( Cervenka et al, 2011 ).…”

Section: Signal Transduction Mediated By Lrp5 and Lrp6mentioning

confidence: 99%

LRP5 and LRP6 in Wnt Signaling: Similarity and Divergence

Ren

Chen

Liu

2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

The canonical Wnt/β-catenin signaling plays a fundamental role in regulating embryonic development, injury repair and the pathogenesis of human diseases. In vertebrates, low density lipoprotein receptor-related proteins 5 and 6 (LRP5 and LRP6), the single-pass transmembrane proteins, act as coreceptors of Wnt ligands and are indispensable for Wnt signal transduction. LRP5 and LRP6 are highly homologous and widely co-expressed in embryonic and adult tissues, and they share similar function in mediating Wnt signaling. However, they also exhibit distinct characteristics by interacting with different protein partners. As such, each of them possesses its own unique functions. In this review, we systematically discuss the similarity and divergence of LRP5 and LRP6 in mediating Wnt and other signaling in the context of kidney diseases. A better understanding of the precise role of LRP5 and LRP6 may afford us to identify and refine therapeutic targets for the treatment of a variety of human diseases.

show abstract

“…c-MET expression is prevalent at the invasive front of the tumor [ 112 ], where the neoplastic cells interact with HGF expressing cancer-associated fibroblasts and macrophages, inducing cell growth and survival, cell motility, and tumor metastasis. c-MET activation might promote WNT signaling inducing stemness on tumor cells [ 113 ], by involving AKT-mediated GSK3β activation and leading to phosphorylation of LRP5/6 and stabilization of β-catenin [ 114 , 115 ].…”

Section: Cancer Stem Cells In Colorectal Cancermentioning

confidence: 99%

Portrait of Cancer Stem Cells on Colorectal Cancer: Molecular Biomarkers, Signaling Pathways and miRNAome

Angius

Scanu

Arru

et al. 2021

IJMS

View full text Add to dashboard Cite

Colorectal cancer (CRC) is a leading cause of cancer death worldwide, and about 20% is metastatic at diagnosis and untreatable. Increasing evidence suggests that the heterogeneous nature of CRC is related to colorectal cancer stem cells (CCSCs), a small cells population with stemness behaviors and responsible for tumor progression, recurrence, and therapy resistance. Growing knowledge of stem cells (SCs) biology has rapidly improved uncovering the molecular mechanisms and possible crosstalk/feedback loops between signaling pathways that directly influence intestinal homeostasis and tumorigenesis. The generation of CCSCs is probably connected to genetic changes in members of signaling pathways, which control self-renewal and pluripotency in SCs and then establish function and phenotype of CCSCs. Particularly, various deregulated CCSC-related miRNAs have been reported to modulate stemness features, controlling CCSCs functions such as regulation of cell cycle genes expression, epithelial-mesenchymal transition, metastasization, and drug-resistance mechanisms. Primarily, CCSC-related miRNAs work by regulating mainly signal pathways known to be involved in CCSCs biology. This review intends to summarize the epigenetic findings linked to miRNAome in the maintenance and regulation of CCSCs, including their relationships with different signaling pathways, which should help to identify specific diagnostic, prognostic, and predictive biomarkers for CRC, but also develop innovative CCSCs-targeted therapies.

show abstract

Hepatocyte Growth Factor (Hgf) Stimulates Low Density Lipoprotein Receptor-related Protein (Lrp) 5/6 Phosphorylation and Promotes Canonical Wnt Signaling

Cited by 23 publications

References 44 publications

Wnt/β-catenin signaling in kidney injury and repair: a double-edged sword

Wnt/β-catenin signaling in kidney injury and repair: a double-edged sword

LRP5 and LRP6 in Wnt Signaling: Similarity and Divergence

Portrait of Cancer Stem Cells on Colorectal Cancer: Molecular Biomarkers, Signaling Pathways and miRNAome

Contact Info

Product

Resources

About