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. 2022 Oct;42(10):1036-1040.
doi: 10.1002/cac2.12338. Epub 2022 Jul 26.

Kindlin-1 drives early steps of breast cancer metastasis

Florian Bonin  1 , Aurélie Chiche  2   3 , Zakia Tariq  1 , Paula Azorin  1 , Sébastien Nola  1   4 , Rosette Lidereau  1 , Keltouma Driouch  1
Affiliations

Kindlin-1 drives early steps of breast cancer metastasis

Florian Bonin et al. Cancer Commun (Lond). 2022 Oct.
No abstract available

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Conflict of interest statement

The authors declare no competing financial interests

Figures

FIGURE 1
FIGURE 1
Kindlin‐1‐mediated local invasion and metastasis require binding to β1‐integrin. (A) Adhesion assay of 168FARN cells expressing Kindlin‐1 (Kind1) or a control vector (Ctrl) on different ECM substrates. FN: Fibronectin, LM 332: Laminin 332, Col 1: Collagen type 1. (B) Flow cytometry analysis of the binding of the fluorescently labeled fibronectin fragment FNIII7‐10 to Ctrl‐ or Kind1‐cells. The staining intensities were normalized as the percentage of binding for ctrl‐cells. (C) Active β1‐integrin expression at the surface of Kind1‐ and ctrl‐cells measured by flow cytometry using the 9EG7 antibody. (D) Immunofluorescence labeling of active β1‐integrin. Scale bar, 20 μm. (E) Western blot analysis of integrin‐signaling effectors. Antibodies specifically recognizing the phosphorylated forms (pSrc and pFAK) and total forms of Src and FAK proteins (Src and FAK) were used. (F) Western blot showing expression of Kindlin1, Kindlin‐2, talin and α5‐integrin in 168FARN cells transfected as indicated. (G) Immunolocalization of active β1‐integrins and EEA1 after internalization and 15 minutes of recycling. Scale bar 20 μm. (H) Three‐dimensional invasion on collagen matrix, representative images of phalloidin (red) and DAPI (blue) staining of 168FARN cells transfected as indicated. Dashed lines delineate embedded spheroid. Scale bar, 20 μm. (I) Growth in tumor volume was quantified by caliper measurements tracking. Error bars indicate mean ± SEM. (J) Representative H&E staining of primary tumors in mice inoculated with control, Kind1 or AAKind1 cells. Scale bar 50 μm. (K) The percentage of KI67‐positive cells was measured in control, Kind1 or AAKind1 tumors. (L) Representative KI67 staining of primary tumors in mice inoculated with control, Kind1 or AAKind1 cells. Scale bar 30 μm. (M) Representative H&E staining of different secondary organs presenting metastatic nodules in mice inoculated with Kind1‐cells. Scale bar 30 μm qRT‐PCR of the hygromycin resistance gene was performed to quantify the number of control, Kind1 or AAKind1 cells that reached secondary organs. (N) Expression heatmap of the most significantly upregulated and downregulated genes in the control vs. Kind1 or AAKind1 tumors. (O) Histogram showing the relative expression of the most upregulated genes in Kind1 tumors in comparison with their expression in control tumors. (P) Histogram showing the relative expression of most upregulated genes in AAKind1 tumors in comparison with their expression in control tumors. (White: control; red: Kind1; blue: AAkind1). Error bars indicate mean ± SEM from three independent experiments. The statistical analyses were performed using the Student's t‐test. The results are considered statistically significant at a P value < 0.05 (*), < 0.01 (**) or < 0.001 (***). Kind1: Kindlin‐1; Ctrl: Control; ECM: Extracellular matrix; FN: Fibronectin; LM: Laminin; Col: Collagen; DAPI: 4′,6‐diamidino‐2èphenylindole; H&E: Hematoxylin and eosin; qRT‐PCR: Quantitative Real Time‐ Polymerase Chain Reaction;; EEA1: early endosomal antigen 1, FC: fold change
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References

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