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Cited by 8Hippo pathway signaling and YAP/TAZCellular Mechanics and InteractionsTGF-β signaling in diseases

Unveiling the mechanistic link between extracellular amyloid fibrils, mechano-signaling and YAP activation in cancer

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Farris, Francesco, Elhagh, Alice, Vigorito, Ilaria, Alongi, Nicoletta, Pisati, Federica, Giannattasio, Michele, Casagrande, Francesca, Veghini, Lisa +5 more·2024·Cell Death & Disease
DOI 10.1038/s41419-024-06424-zPMC PMC10781709
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Abstract

The tumor microenvironment is a complex ecosystem that plays a critical role in cancer progression and treatment response. Recently, extracellular amyloid fibrils have emerged as novel components of the tumor microenvironment; however, their function remains elusive. In this study, we establish a direct connection between the presence of amyloid fibrils in the secretome and the activation of YAP, a transcriptional co-activator involved in cancer proliferation and drug resistance. Furthermore, we uncover a shared mechano-signaling mechanism triggered by amyloid fibrils in both melanoma and pancreatic ductal adenocarcinoma cells. Our findings highlight the crucial role of the glycocalyx protein Agrin which binds to extracellular amyloid fibrils and acts as a necessary factor in driving amyloid-dependent YAP activation. Additionally, we reveal the involvement of the HIPPO pathway core kinase LATS1 in this signaling cascade. Finally, we demonstrate that extracellular amyloid fibrils enhance cancer cell migration and invasion. In conclusion, our research expands our knowledge of the tumor microenvironment by uncovering the role of extracellular amyloid fibrils in driving mechano-signaling and YAP activation. This knowledge opens up new avenues for developing innovative strategies to modulate YAP activation and mitigate its detrimental effects during cancer progression.

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  • Extracellular amyloid fibrils modulate mechanosignaling and influence the physical and biochemical properties of tumor niches in melanoma and pancreatic ductal adenocarcinoma cells, thereby promoting tumor cell migration and invasion.

    “These fibrils have been shown to modulate mechanosignaling and influence the physical and biochemical properties of tumor niches in both melanoma and pancreatic ductal adenocarcinoma cells, thereby promoting tumor cells migration and invasion6.”

    From Oligomeric cystatin C supports the immunosuppressive activity of myeloid cells through interaction with inhibitory receptors (2025) · cites this paper as [6]

    The Results section reports that amyloid fibrils activate YAP through a glycocalyx–HIPPO signaling axis in melanoma and pancreatic cancer, promoting cell migration and invasion. The Discussion describes the fibrils as a mechanical stimulus in the tumor microenvironment, but does not establish that they change the physical and biochemical properties of tumor niches; it says the basis of their mechanical recognition remains unclear. No page numbers are available in our copy. (LLM, conf=0.82)

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Cited by

Sorted by citations

Authors
Farris, F., Elhagh, A., Vigorito, I., Alongi, N., Pisati, F., Giannattasio, M., Casagrande, F., Veghini, L., Corbo, V., Tripodo, C., Di Napoli, A., Matafora, V., & Bachi, A.
Affiliations
  • IFOM (IT)
  • Cogentech S.R.L. Società Benefit a Socio Unico soggetta all’attività di direzione e coordinamento di IFOM - Istituto Fondazione di Oncologia Molecolare ETS (Italy) (IT)
  • University of Milan (IT)
  • University of Verona (IT)
Corresponding author
  • Matafora, Vittoria
  • Bachi, Angela
ORCID
Venue
Cell Death & Disease
Publisher
Springer Science and Business Media LLC
Published
2024-01-11
Volume
15
Issue
1
Pages
28-28
ISSN
2041-4889 (ISSN-L)
DOI
10.1038/s41419-024-06424-z
PMC
PMC10781709
OpenAlex
W4390718142
Cited by
8
References
3
Citations by year
2026: 1 · 2025: 7
FWCI
1.79
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Death and Disease (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
  • IRIS UniPA (University of Palermo) (submittedVersion, other-oa)
  • IRIS Research product catalog (Sapienza University of Rome) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Associazione Italiana per la Ricerca sul Cancro (IG 27098, IG 18607)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
Keywords
YAP activation, tumor microenvironment, agrin, LATS1, Hippo signaling pathway, melanoma, pancreatic ductal adenocarcinoma, tumor cell migration and invasion, drug resistance
MeSH terms
Amyloid, Humans, Melanoma, Pancreatic Neoplasms, Signal Transduction, Ecosystem, Tumor Microenvironment

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