WNT Ligand Dependencies in Pancreatic Cancer

Aguilera, Kristina Y.; Dawson, David W.

doi:10.3389/fcell.2021.671022

Cited by 34 publications

(35 citation statements)

References 74 publications

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“…1 C). The growth factor receptors and frizzled receptors are well characterized as contributors to PDAC tumor development [ 18 , 19 ]. The formyl peptide receptors are expressed in phagocytes and a recent study showed that the ANXA1 – FPRs pathway promotes PDAC metastasis [ 20 ].…”

Section: Resultsmentioning

confidence: 99%

Cell-to-cell interaction analysis of prognostic ligand-receptor pairs in human pancreatic ductal adenocarcinoma

Suzuki

Kuno

Ozaki

2021

Biochemistry and Biophysics Reports

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Cell-to-cell interactions (CCIs) through ligand-receptor (LR) pairs in the tumor microenvironment underlie the poor prognosis of pancreatic ductal adenocarcinoma (PDAC). However, there is scant knowledge of the association of CCIs with PDAC prognosis, which is critical to the identification of potential therapeutic candidates. Here, we sought to identify the LR pairs associated with PDAC patient prognosis by integrating survival analysis and single-cell CCI prediction. Via survival analysis using gene expression from cancer cohorts, we found 199 prognostic LR pairs. CCI prediction based on single-cell RNA-seq data revealed the enriched LR pairs associated with poor prognosis. Notably, the CCIs involved epithelial tumor cells, cancer-associated fibroblasts, and tumor-associated macrophages through integrin-related and ANXA1 – FPR pairs. Finally, we determined that CCIs involving 33 poor-prognostic LR pairs were associated with tumor grade. Although the clinical implication of the set of LR pairs must be determined, our results may provide potential therapeutic targets in PDAC.

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Section: Resultsmentioning

confidence: 99%

Cell-to-cell interaction analysis of prognostic ligand-receptor pairs in human pancreatic ductal adenocarcinoma

Suzuki

Kuno

Ozaki

2021

Biochemistry and Biophysics Reports

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“…DpC also inhibited PSC activation in vitro and reduced desmoplasia in vivo ( 48 ). The current study mechanistically dissected for the first time the effects of the metastasis suppressor, NDRG1, and the NDRG1-inducing thiosemicarbazones on more recently identified key mediators of cross talk between PC cells and PSCs, namely TGF-β, TnC, Wnt/β-catenin, and YAP/TAZ ( 12 , 97 , 114 , 115 , 116 ). In fact, TnC is highly elevated in invasive PC and produced by activated PSCs ( 35 , 117 ), leading to activation of oncogenic Wnt/β-catenin and YAP/TAZ pathways ( Fig.…”

Section: Discussionmentioning

confidence: 99%

Targeting Wnt/tenascin C-mediated cross talk between pancreatic cancer cells and stellate cells via activation of the metastasis suppressor NDRG1

Geleta

Tout

Lim

et al. 2022

Journal of Biological Chemistry

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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“…WNT ligand signaling plays key roles in PDAC initiation, progression, dissemination, and therapeutic resistance. Therapeutic interest is a genetically defined subset of PDAC known to have increased WNT/β‐catenin transcriptional activity, growth dependency on WNT ligand signaling, and response to pharmacologic inhibitors of the WNT pathway (Aguilera & Dawson, 2021).…”

Section: Discussionmentioning

confidence: 99%

Wnt signaling pathway: A comprehensive review

Hayat

Manzoor

Hussain

2022

Cell Biology International

119

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Wnt signaling is an evolutionary cell‐to‐cell coordination mechanism and it is highly critical for a variety of physiological processes of an organism's body, including stem cell regeneration, proliferation, division, migration, polarity of a cell, determining fate of the cell and specification of neural crest, neural symmetry and morphogenesis. Wnts are extracellular secreted glycol proteins, consisted of a family of 19 human proteins that represent the complex nature of the regulatory structure and physiological efficiency of signaling. Moreover, a Wnt/β‐catenin‐dependent pathway and the β‐catenin‐independent pathway that is further classified into the Planar Cell Polarity and Wnt/Ca2+ pathways have been established as key signaling nodes downstream of the frizzled (Fz/Fzd) receptor, and these nodes are extensively analyzed at biochemical and molecular levels. Genetic and epigenetic activities that ultimately characterize the pathway and its subsequent responses contribute to Wnt‐β‐catenin signaling pathway hypo or hyper‐activation and is associated with the variety of human disorders progression most significantly cancers. Recognizing how this mechanism operates is crucial to the advancement of cancer prevention therapies or regenerative medicine methods.

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WNT Ligand Dependencies in Pancreatic Cancer

Cited by 34 publications

References 74 publications

Cell-to-cell interaction analysis of prognostic ligand-receptor pairs in human pancreatic ductal adenocarcinoma

Cell-to-cell interaction analysis of prognostic ligand-receptor pairs in human pancreatic ductal adenocarcinoma

Targeting Wnt/tenascin C-mediated cross talk between pancreatic cancer cells and stellate cells via activation of the metastasis suppressor NDRG1

Wnt signaling pathway: A comprehensive review

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