Asano Y, Kishida S, Mu P, Sakamoto K, Murohara T, Kadomatsu K . DRR1 is expressed in the developing nervous system and downregulated during neuroblastoma carcinogenesis. Biochem Biophys Res Commun 2010; 394: 829–835. a) Immunoblotting of DDR1, DDR2 and loading control β-ACTIN in M-Wnt and AT-3 Ddr1-WT/KO tumour cells. Images are representatives of three independent experiments. ( b–d) In vitro cell proliferation of E0771 (WT: n = 3, KO: n = 5, b), M-Wnt (WT: n = 3, KO: n = 5, c) and AT-3 (WT: n = 6, KO: n = 4, d) tumour cells, n indicate technical repeats. Out of three biological repeats. ( e–f) M-Wnt (n = 4 tumours/group, e) and AT-3 (n = 5 tumours/group, f) tumour growth in immunodeficient mice. ( g–h) M-Wnt (n = 7 tumours/group, g) and AT-3 (n = 7 tumours/group, h) tumour growth in immunocompetent C57BL/6 mice. ( i–j) M-Wnt and AT-3 tumours were grown firstly in Rag1 −/− hosts. Approximately 60 mg of tumour pieces were transplanted to C57BL/6 mice. Tumour volume of M-Wnt (WT” n = 9 tumours, KO: n = 10 tumours, i) and AT-3 (WT: n = 10 tumours, KO: n = 9 tumours, j). ( k) Percentage of CD8 + in CD3 + T cells in blood, n = 5 mice/group. ( l) Tumour volumes in C57BL/6 hosts with prior treatment of anti-IgG or anti-CD8 antibody (n = 5 tumours/group). ( m) CD8 + TILs normalized by tumour weight in Rag1 −/− mice after adoptive transfer of CD8 + T cells or medium (sham), n = 6 tumours/group. ( n) Tumour volumes in Rag1 −/− mice after adoptive transfer of CD8 + T cells or medium (sham). n = 6 tumours/group. Arrow indicates transfer of CD8 + T cells on day 17. ( o) Tumour weight from rechallenged mice (n = 6 tumours/group). Values represent mean ± SEM. p value and n as indicated, all tests used two-way ANOVA except for CD8 + quantification, which used two-tailed Student’s t-test. Salmon, H. et al. Matrix architecture defines the preferential localization and migration of T cells into the stroma of human lung tumors. J. Cell. Invest. 122, 899–910 (2021). Yamazaki S, Yamamoto K, de Lanerolle P, Harata M . Nuclear F-actin enhances the transcriptional activity of beta-catenin by increasing its nuclear localization and binding to chromatin. Histochem Cell Biol 2016; 145: 389–399. Kishida S, Mu P, Miyakawa S, Fujiwara M, Abe T, Sakamoto K et al. Midkine promotes neuroblastoma through Notch2 signaling. Cancer Res 2013; 73: 1318–1327.

Raudvere, U. et al. g:Profiler: a web server for functional enrichment analysis and conversions of gene lists. Nucleic Acids Res. 47, W191–W198 (2019). a) E0771 Ddr1-WT/KO tumours transplanted from Rag1 −/− to C57BL/6 hosts were analysed by SHG, To-pro-3 staining for all nuclei, and collagen fibre individualization. Scale bar: 50 µm. ( b, c) M-Wnt (WT n = 8 tumours, KO n = 4 tumours) and AT-3 (n = 5 tumours/group) Ddr1-WT/KO tumours transplanted from Rag1 −/− to C57BL/6 hosts were analysed for infiltrating CD3 + T cells normalized by total cells via IHC. ( d–g) M-Wnt and AT-3 Ddr1-WT/KO tumours transplanted from Rag1 −/− to C57BL/6 hosts were analysed for collagen fibre alignment (d, e) and fibre length (f, g), n = 4 tumours/group. ( h–j) E0771, n = 5 tumours/group (h), M-Wnt, n = 4 tumours/group (i) and AT-3, n = 4/group (j) Ddr1-WT/KO tumours transplanted from Rag1 −/− to C57BL/6 hosts were analysed for fibre numbers by the CT-Fire software. ( k–m) E0771 Ddr1-WT/KO tumours (WT n = 10 tumours, KO n = 8 tumours) from immunodeficient Rag1 −/− hosts were analysed for collagen fibre alignment (k), fibre length (l) and fibre numbers (m) by the CT-Fire software. ( n) Growth curves of E0771 Ddr1-KO tumours in immunocompetent hosts that were intratumorally injected with recombinant WT and mutant Fc-ECD (WT: n = 10 tumours, W54A: n = 9 tumours). ( o) Representative images of E0771 Ddr1-KO tumours treated with recombinant WT or mutant Fc-ECD in C57BL/6 hosts as analysed by SHG, To-pro-3 staining, and collagen fibre individualization. Scale bar: 50 µm. ( p) Quantification of collagen fibre alignment in WT and mutant Fc-ECD treated tumours (n = 5 tumours/group). ( q) Enumeration of infiltrating CD3 + T cells normalized by total cells via IHC (WT: n = 4 tumours, KO: n = 3 tumours). Values represent mean ± SEM. p value as indicated, two-tailed Student’s t-test for all tests except for tumour volumes, which were done by two-way ANOVA.Rheumatology Department and Rheumatology Research Group, Vall d’Hebron Hospital Research Institute, Barcelona, Spain Xia PY, Wang S, Huang GL, Zhu PP, Li M, Ye BQ et al. WASH is required for the differentiation commitment of hematopoietic stem cells in a c-Myc-dependent manner. J Exp Med 2014; 211: 2119–2134. Ray, A. & Provenzano, P. P. Aligned forces: Origins and mechanisms of cancer dissemination guided by extracellular matrix architecture. Curr. Opin. Cell Biol. 72, 63–71 (2021).

the UK.). They are also a good way to go if you are looking to retrain and take your life in a brand new direction. Leitinger, B. Discoidin domain receptor functions in physiological and pathological conditions. Int. Rev. Cell Mol. Biol. 310, 39–87 (2014). Vogel, W. F., Aszodi, A., Alves, F. & Pawson, T. Discoidin domain receptor 1 tyrosine kinase has an essential role in mammary gland development. Mol. Cell. Biol. 21, 2906–2917 (2001).

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Baarlink C, Wang H, Grosse R . Nuclear actin network assembly by formins regulates the SRF coactivator MAL. Science 2013; 340: 864–867. Takai, K. et al. Discoidin domain receptor 1 (DDR1) ablation promotes tissue fibrosis and hypoxia to induce aggressive basal-like breast cancers. Genes Dev. 32, 244–257 (2018). Redruth town mayor, Councillor Deborah Reevem said: “This is an excellent show of confidence in the Redruth economy. We welcome the investment into our community and the employment opportunities that this will create.”

Geng H, Wittwer T, Dittrich-Breiholz O, Kracht M, Schmitz ML . Phosphorylation of NF-kappaB p65 at Ser468 controls its COMMD1-dependent ubiquitination and target gene-specific proteasomal elimination. EMBO Rep 2009; 10: 381–386.Muller PA, van de Sluis B, Groot AJ, Verbeek D, Vonk WI, Maine GN et al. Nuclear-cytosolic transport of COMMD1 regulates NF-kappaB and HIF-1 activity. Traffic 2009; 10: 514–527.