title: A specific STAT3-binding peptide exerts antiproliferative effects and antitumor activity by inhibiting STAT3 phosphorylation and signaling.
abstract: STAT3 promotes the survival, proliferation, metastasis, immune escape, and drug resistance of cancer cells, making its targeting an appealing prospect. However, although multiple inhibitors of STAT3 and its regulatory or effector pathway elements have been developed, bioactive agents have been somewhat elusive. In this report, we report the identification of a specific STAT3-binding peptide (APTSTAT3) through phage display of a novel "aptide" library. APTSTAT3 bound STAT3 with high specificity and affinity (∼231 nmol/L). Addition of a cell-penetrating motif to the peptide to yield APTSTAT3-9R enabled uptake by murine B16F1 melanoma cells. Treatment of various types of cancer cells with APTSTAT3-9R blocked STAT3 phosphorylation and reduced expression of STAT targets, including cyclin D1, Bcl-xL, and survivin. As a result, APTSTAT3-9R suppressed the viability and proliferation of cancer cells. Furthermore, intratumoral injection of APTSTAT3-9R exerted potent antitumor activity in both xenograft and allograft tumor models. Our results offer a preclinical proof-of-concept for APTSTAT3 as a tractable agent for translation to target the broad array of cancers harboring constitutively activated STAT3.
authors.affiliation: Authors' Affiliation: KAIST Institute for the BioCentury, Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
authors.forename: Daejin
authors.initials: D
authors.lastname: Kim
authors.forename: In-Hyun
authors.initials: IH
authors.lastname: Lee
authors.forename: Sunghyun
authors.initials: S
authors.lastname: Kim
authors.forename: Minsuk
authors.initials: M
authors.lastname: Choi
authors.forename: Hyungjun
authors.initials: H
authors.lastname: Kim
authors.forename: Sukyung
authors.initials: S
authors.lastname: Ahn
authors.forename: Phei Er
authors.initials: PE
authors.lastname: Saw
authors.forename: Hyungsu
authors.initials: H
authors.lastname: Jeon
authors.forename: Yumi
authors.initials: Y
authors.lastname: Lee
authors.forename: Sangyong
authors.initials: S
authors.lastname: Jon
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D015398:Signal Transduction; D013379:Substrate Specificity; D023041:Xenograft Model Antitumor Assays
chemical_list: D010455:Peptides; D050796:STAT3 Transcription Factor