Inhibition of peptidyl-prolyl isomerase (PIN1) and BRAF signaling to target melanoma

Braun C, Schneider N, Pei D, Boßerhoff AK, Kuphal S (2019)

Publication Type: Journal article

Publication year: 2019

Journal

American Journal of Translational Research e-Century Publishing

Book Volume: 11

Pages Range: 4425-+

Journal Issue: 7

Abstract

PIN1 is a phosphorylation-dependent peptidyl-prolyl cis/trans isomerase, overexpressed in many cancers, including melanoma. Our immunohistochemistry data of melanoma patient tissue underline the up-regulation of PIN1 in metastases. Here, we demonstrate important functions of PIN1 and its selective and cell permeable inhibitor 37 for the treatment of melanoma. To analyze its possible role in oncogenesis and as a therapeutic target, we first suppressed PIN1 expression by a siRNA pool. PIN1 knockdown potently inhibited melanoma cell proliferation and vascular mimicry by influencing several cancer-relevant pathways. Furthermore, inhibitor 37 inhibited cell growth in melanoma and induced apoptosis. Normal healthy melanocytes, keratinocytes and fibroblasts are not affected by the PIN1 inhibitor 37. Combinatorial treatment of melanoma cells is with Vemurafenib as a common therapeutic option for BRAF-mutated melanoma and inhibitor 37 resulted in a strong, synergistic effect on apoptosis of melanoma cell lines. In summary, targeting PIN1 offers a promising therapeutic approach to simultaneously downregulate multiple cancer-driving pathways in cancer.

Authors with CRIS profile

Nadja Schneider Lehrstuhl für Biochemie und Molekulare Medizin Anja Katrin Boßerhoff Lehrstuhl für Biochemie und Molekulare Medizin Silke Kuphal Lehrstuhl für Biochemie und Molekulare Medizin

Involved external institutions

Ohio State University US United States (USA) (US)

How to cite

APA:

Braun, C., Schneider, N., Pei, D., Boßerhoff, A.K., & Kuphal, S. (2019). Inhibition of peptidyl-prolyl isomerase (PIN1) and BRAF signaling to target melanoma. American Journal of Translational Research, 11(7), 4425-+.

MLA:

Braun, Christina, et al. "Inhibition of peptidyl-prolyl isomerase (PIN1) and BRAF signaling to target melanoma." American Journal of Translational Research 11.7 (2019): 4425-+.

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