Targeting Chaperonin Containing Tcp1 (Cct) As A Molecular Therapeutic For Small Cell Lung Cancer

Keywords

chaperoneLung cancer; PeptideSTAT3Nanoparticles

Abstract

Identifying new druggable targets is desired to meet the needs for effectivecancer treatments. To this end, we previously reported the efficacy of a therapeuticpeptide called CT20p that displays selective cytotoxicity through inhibition of a multisubunit,protein-folding complex called Chaperonin-Containing TCP-1 (CCT). Toinvestigate the role of CCT in cancer progression, we examined protein levels of CCTsubunits in liver, prostate, and lung cancer using human tissue microarrays. We foundthat these cancers expressed higher levels of CCT2 as compared to normal tissues.Small cell lung cancer (SCLC) stood out as having statistically significant difference inCCT2. Higher levels of CCT2 in tumors from lung cancer patients were also associatedwith decreased survival. Using SCLC cell lines, we observed detectable amounts ofCCT subunits and cells were susceptible to killing by CT20p. Treatment with CT20p,delivered to cells using polymeric nanoparticles, was cytotoxic to all SCLC cell lines,decreasing the levels of CCT client proteins like STAT3. In contrast, treatment witha STAT3 inhibitor was effective in one of the SCLC cell lines. While we found thatCCT levels could vary in cell lines, normal tissues had low levels of CCT and minimaltoxicity to liver or kidney function was observed in mice treated with CT20p. Theseresults indicate that in SCLC, changes in CCT levels could be used as a biomarker fordiagnosis and that targeting CCT for inhibition with CT20p is a promising treatmentApproach for those cancers such as SCLC that currently lack targeted therapeutics.

Publication Date

1-1-2017

Publication Title

Oncotarget

Volume

8

Issue

66

Number of Pages

110273-110288

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.18632/oncotarget.22681

Socpus ID

85038081134 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/85038081134

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