Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Dickkopf-3 links HSF1 and YAP/TAZ signalling to control aggressive behaviours in cancer-associated fibroblasts

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Shared heritability and functional enrichment across six solid cancers

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Joint sequencing of human and pathogen genomes reveals the genetics of pneumococcal meningitis

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Low-frequency variation in TP53 has large effects on head circumference and intracranial volume

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. The splicing factor RBM25 controls MYC activity in acute myeloid leukemia

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. Author Correction: Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Tumour-reactive T cell subsets in the microenvironment of ovarian cancer

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. T cells isolated from patients with checkpoint inhibitor-resistant melanoma are functional and can mediate tumor regression

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. T-cell Responses in the Microenvironment of Primary Renal Cell Carcinoma-Implications for Adoptive Cell Therapy

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Adoptive cell therapy with tumor-infiltrating lymphocytes in patients with metastatic ovarian cancer: a pilot study

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. 13PD T cell responses in patients with melanoma resistant to multiple immunotherapies

    Research output: Contribution to journalJournal articleResearchpeer-review

  • Nicola Ferrari
  • Romana Ranftl
  • Ievgeniia Chicherova
  • Neil D. Slaven
  • Emad Moeendarbary
  • Aaron J. Farrugia
  • Maxine Lam
  • Maria Semiannikova
  • Marie C.W. Westergaard
  • Julia Tchou
  • Luca Magnani
  • Fernando Calvo
View graph of relations

Aggressive behaviours of solid tumours are highly influenced by the tumour microenvironment. Multiple signalling pathways can affect the normal function of stromal fibroblasts in tumours, but how these events are coordinated to generate tumour-promoting cancer-associated fibroblasts (CAFs) is not well understood. Here we show that stromal expression of Dickkopf-3 (DKK3) is associated with aggressive breast, colorectal and ovarian cancers. We demonstrate that DKK3 is a HSF1 effector that modulates the pro-tumorigenic behaviour of CAFs in vitro and in vivo. DKK3 orchestrates a concomitant activation of β-catenin and YAP/TAZ. Whereas β-catenin is dispensable for CAF-mediated ECM remodelling, cancer cell growth and invasion, DKK3-driven YAP/TAZ activation is required to induce tumour-promoting phenotypes. Mechanistically, DKK3 in CAFs acts via canonical Wnt signalling by interfering with the negative regulator Kremen and increasing cell-surface levels of LRP6. This work reveals an unpredicted link between HSF1, Wnt signalling and YAP/TAZ relevant for the generation of tumour-promoting CAFs.

Original languageEnglish
Article number130
JournalNature Communications
Volume10
Issue number1
ISSN2041-1723
DOIs
Publication statusPublished - 1 Dec 2019

ID: 56749526