Mimetics of suppressor of cytokine signaling 3: Novel potential therapeutics in triple breast cancer

International Journal of Cancer. Journal International Du Cancer
Sara La MannaDaniela Marasco

Abstract

Suppressor of cytokine signaling (SOCS) family of proteins plays critical role in the regulation of immune responses controlling JAK/STAT mediated inflammatory cytokines. Among the members, SOCS1 and SOCS3 contain a kinase inhibitory region (KIR) and SOCS3 binds to JAK/STAT/gp130 complex by inhibiting the downstream signaling and suppressing inflammatory cytokines. Loss or reduced levels of SOCS3 have been linked to cancer-associated inflammation and suppressive immunity leading to enhanced tumor growth and metastasis. In line with these reports, we previously demonstrated that proteolytic degradation of SOCS3 in triple negative breast cancer (TNBC) subtype drives the expression of inflammatory cytokines. Therefore, we postulated that SOCS3 mimetics might suppress the inflammatory cytokine production in TNBC subtype and inhibit tumor growth and metastasis. Here we designed and characterized five linear peptides derived from the N-terminal region of SOCS3 encompassing regions that interface with the JAK2/gp130 complex using the Circular Dichroism and Surface Plasmon Resonance spectroscopies. The KIRESS peptide resulted the sequence containing the most part of the hot-spots required for binding to JAK2 and was further investigate...Continue Reading

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Citations

May 16, 2019·Neural Regeneration Research·Yi LiXiao-Dong Wang
Sep 14, 2018·International Journal of Molecular Sciences·Sara La MannaDaniela Marasco
May 22, 2020·ACS Medicinal Chemistry Letters·Sara La MannaDaniela Marasco
Oct 8, 2021·Physical Chemistry Chemical Physics : PCCP·Cristina CantaruttiSara Fortuna

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