Supplemental Figures S1-S5 from SYK Is a Candidate Kinase Target for the Treatment of Advanced Prostate Cancer

Ghotra, Veerander P.S.; He, Shuning; van der Horst, Geertje; Nijhoff, Steffen; de Bont, Hans; Lekkerkerker, Annemarie; Janssen, Richard; Jenster, Guido; van Leenders, Geert J.L.H.; Hoogland, A. Marije M.; Verhoef, Esther I.; Baranski, Zuzanna; Xiong, Jiangling; van de Water, Bob; van der Pluijm, Gabri; Snaar-Jagalska, B. Ewa; Danen, Erik H.J.

doi:10.1158/0008-5472.22405436.v1

Supplemental Figures S1-S5 from SYK Is a Candidate Kinase Target for the Treatment of Advanced Prostate Cancer

journal contribution

posted on 2023-03-30, 23:06 authored by Veerander P.S. Ghotra, Shuning He, Geertje van der Horst, Steffen Nijhoff, Hans de Bont, Annemarie Lekkerkerker, Richard Janssen, Guido Jenster, Geert J.L.H. van Leenders, A. Marije M. Hoogland, Esther I. Verhoef, Zuzanna Baranski, Jiangling Xiong, Bob van de Water, Gabri van der Pluijm, B. Ewa Snaar-Jagalska, Erik H.J. Danen

Supplemental Figures S1-S5 Figure S1. Whole organism automated bioimaging assay differentiates between androgen independent / metastatic and androgen-dependent / non-metastatic prostate cancer cells. Figure S2. SYK depletion attenuates PC3 dissemination in zebrafish xenografts. Figure S3. Reduced protein expression of SYK in PC3shSYK cells. Figure S4. SYK depletion attenuates PC3 3D ECM invasion. Figure S5. SYK depletion attenuates colony formation but does not affect AKT activity or CD44 protein expression.

History

ARTICLE ABSTRACT

Improved targeted therapies are needed to combat metastatic prostate cancer. Here, we report the identification of the spleen kinase SYK as a mediator of metastatic dissemination in zebrafish and mouse xenograft models of human prostate cancer. Although SYK has not been implicated previously in this disease, we found that its expression is upregulated in human prostate cancers and associated with malignant progression. RNAi-mediated silencing prevented invasive outgrowth in vitro and bone colonization in vivo, effects that were reversed by wild-type but not kinase-dead SYK expression. In the absence of SYK expression, cell surface levels of the progression-associated adhesion receptors integrin α2β1 and CD44 were diminished. RNAi-mediated silencing of α2β1 phenocopied SYK depletion in vitro and in vivo, suggesting an effector role for α2β1 in this setting. Notably, pharmacologic inhibitors of SYK kinase currently in phase I–II trials for other indications interfered similarly with the invasive growth and dissemination of prostate cancer cells. Our findings offer a mechanistic rationale to reposition SYK kinase inhibitors for evaluation in patients with metastatic prostate cancer. Cancer Res; 75(1); 230–40. ©2014 AACR.