Cancer-associated fibroblast-derived ROR2 induces WNT/PCP activation and polarized migration in receiving gastric cancer cells

Rogers, Sally; Zhang, Chengting; Anagnostidis, Vasilis; Fishel, Melissa L.; Gielen, Fabrice; Scholpp, Steffen

doi:10.1101/2022.04.07.487474

Cited by 2 publications

(2 citation statements)

References 36 publications

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“…Furthermore, in human glioma cells EGFRvIII is distributed by extracellular vesicle-based transfer to activate other membrane-associated oncogenic tyrosine kinases such as HER2, KIT and MET 57 . Our group recently demonstrated that ROR2 and WNT5A are significantly correlated on cytonemes of human cancer-associated fibroblasts; in the same study, ROR2 was identified in the cytoneme-receiving gastric tumour cells influencing migration of gastric cancer cells 58 , suggesting a conserved signalling role in vertebrate embryogenesis and disease.…”

Section: Discussionmentioning

confidence: 79%

Cytoneme-mediated transport of active Wnt5b–Ror2 complexes in zebrafish

Zhang,

Brunt,

Ono

et al. 2023

Nature

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Chemical signalling is the primary means by which cells communicate in the embryo. The underlying principle refers to a group of ligand-producing cells and a group of cells that respond to this signal because they express the appropriate receptors1,2. In the zebrafish embryo, Wnt5b binds to the receptor Ror2 to trigger the Wnt–planar cell polarity (PCP) signalling pathway to regulate tissue polarity and cell migration3,4. However, it remains unclear how this lipophilic ligand is transported from the source cells through the aqueous extracellular space to the target tissue. In this study, we provide evidence that Wnt5b, together with Ror2, is loaded on long protrusions called cytonemes. Our data further suggest that the active Wnt5b–Ror2 complexes form in the producing cell and are handed over from these cytonemes to the receiving cell. Then, the receiving cell has the capacity to initiate Wnt–PCP signalling, irrespective of its functional Ror2 receptor status. On the tissue level, we further show that cytoneme-dependent spreading of active Wnt5b–Ror2 affects convergence and extension in the zebrafish gastrula. We suggest that cytoneme-mediated transfer of ligand–receptor complexes is a vital mechanism for paracrine signalling. This may prompt a reevaluation of the conventional concept of characterizing responsive and non-responsive tissues solely on the basis of the expression of receptors.

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Section: Discussionmentioning

confidence: 79%

Cytoneme-mediated transport of active Wnt5b–Ror2 complexes in zebrafish

Zhang,

Brunt,

Ono

et al. 2023

Nature

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show abstract

“…In a parallel study by our group, we provide further evidence that in gastric cancer, ROR2, and the relevant ligand WNT5A are significantly correlated on cytoneme in human cancer-associated fibroblasts. We also identify these clusters in the cytoneme-receiving gastric tumor cells (Rogers et al, 2022). Moreover, cytoneme-dependent spreading of WNT5A/ROR2 complexes is critical for polarization and directed migration of the gastric cancer cells.…”

Section: Discussionmentioning

confidence: 91%

Cytoneme-mediated transport of active Wnt5b/Ror2 complexes in zebrafish gastrulation

Zhang

Brunt

Rogers

et al. 2022

Preprint

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Chemical signaling is the primary means by which cells communicate in the embryo. The underlying principle refers to a group of ligand-producing cells and a group of cells that respond to this signal because they express the appropriate receptors. In the zebrafish embryo, Wnt5b binds to the receptor Ror2 to trigger the Wnt/Planar Cell Polarity (Wnt/PCP) signaling pathway to regulate tissue polarity and cell migration. However, it is still unclear how this lipophilic ligand is transported from the source cells through the aqueous extracellular space to the target tissue. Here we show that Wnt5b, together with Ror2, is loaded on long protrusions. The active Wnt5b/Ror2 complexes are handed over from these cytonemes to the receiving cell to trigger Wnt/PCP signaling, regardless of whether the cell expresses functional receptors. On the tissue level, we show that cytoneme-dependent spreading of active Wnt5b/Ror2 affects convergence and extension in the zebrafish gastrula.

show abstract

Cancer-associated fibroblast-derived ROR2 induces WNT/PCP activation and polarized migration in receiving gastric cancer cells

Cited by 2 publications

References 36 publications

Cytoneme-mediated transport of active Wnt5b–Ror2 complexes in zebrafish

Cytoneme-mediated transport of active Wnt5b–Ror2 complexes in zebrafish

Cytoneme-mediated transport of active Wnt5b/Ror2 complexes in zebrafish gastrulation

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