Skip to main content
. Author manuscript; available in PMC: 2014 Oct 1.
Published in final edited form as: Nat Med. 2014 Mar 30;20(4):350–359. doi: 10.1038/nm.3490

Figure 6.

Figure 6

Loss of Kindlin-1 increases skin tumor incidence. (a–e) Two stage carcinogenesis (n=26 Control and 23 Kind1-K5 mice). (a) Tumor incidence (P-value by log-rank test), (b) burden and (c) skin lesions per animal (reported as mean ± SD) after 25 weeks of treatment. (d) Tumor growth reported as diameter is shown in a boxplot where whisker ends are at 1.5 interquartile ranges and middle lines represent the median. (e) The percentage of skin lesion subtypes from control (n=25 lesions) and Kind1-K5 mice (n=47 lesions) were staged by histology and immunofluorescence analysis (see Supplementary Fig. 8a). (f–i) One stage carcinogenesis with DMBA. (f) Tumor incidence, (g) skin lesion number, (h) frequency and (i) size of control (n=10) and Kind1-K5 (n=10) mice monitored as in (a–d). (j) Molecular functions of Kindlin-1; in normal cells (left panel) Kindlin-1 activates β1-class integrins and αvβ6 integrin to facilitate adhesion and TGFβ liberation from LAP, respectively. Free TGFβ activates TGFβ receptors (TβRI/II) leading to nuclear translocation of phosphorylated Smad2/3, which promotes SC quiescence. In Kindlin-1 deficient cells (right panel) activation of β1-class integrins and αvβ6 is impaired leading to adhesion defects and loss of TGFβ-mediated SC quiescence. In addition, dysregulated Wnt ligand expression leading to elevation of Wnt5a leads to canonical Wnt-β-catenin signaling via the Lrp5/6-Fzd4 complex. Wnt5-Prom, Wnt5 promotor.