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Journal article
v-Src Oncogene Induces Trop2 Proteolytic Activation via Cyclin D1
Cancer research (Chicago, Ill.), v 76(22), pp 6723-6734
15 Nov 2016
PMID: 27634768
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Proteomic analysis of castration-resistant prostate cancer demonstrated the enrichment of Src tyrosine kinase activity in approximately 90% of patients. Src is known to induce cyclin D1, and a cyclin D1-regulated gene expression module predicts poor outcome in human prostate cancer. The tumor-associated calcium signal transducer 2 (TACSTD2/Trop2/M1S1) is enriched in the prostate, promoting prostate stem cell self-renewal upon proteolytic activation via a γ-secretase cleavage complex (PS1, PS2) and TACE (ADAM17), which releases the Trop2 intracellular domain (Trop2 ICD). Herein, v-Src transformation of primary murine prostate epithelial cells increased the proportion of prostate cancer stem cells as characterized by gene expression, epitope characteristics, and prostatosphere formation. Cyclin D1 was induced by v-Src, and Src kinase induction of Trop2 ICD nuclear accumulation required cyclin D1. Cyclin D1 induced abundance of the Trop2 proteolytic cleavage activation components (PS2, TACE) and restrained expression of the inhibitory component of the Trop2 proteolytic complex (Numb). Patients with prostate cancer with increased nuclear Trop2 ICD and cyclin D1, and reduced Numb, had reduced recurrence-free survival probability (HR = 4.35). Cyclin D1, therefore, serves as a transducer of v-Src-mediated induction of Trop2 ICD by enhancing abundance of the Trop2 proteolytic activation complex. Cancer Res; 76(22); 6723-34. ©2016 AACR.
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- Title
- v-Src Oncogene Induces Trop2 Proteolytic Activation via Cyclin D1
- Creators
- Xiaoming Ju - Thomas Jefferson UniversityXuanmao Jiao - Thomas Jefferson UniversityAdam Ertel - Thomas Jefferson UniversityMathew C Casimiro - Thomas Jefferson UniversityGabriele Di Sante - Thomas Jefferson UniversityShengqiong Deng - Thomas Jefferson UniversityZhiping Li - Thomas Jefferson UniversityAgnese Di Rocco - Thomas Jefferson UniversityTingting Zhan - Thomas Jefferson UniversityAdam Hawkins - Thomas Jefferson UniversityTanya Stoyanova - University of California, Los AngelesSebastiano Andò - University of CalabriaAlessandro Fatatis - Drexel UniversityMichael P Lisanti - Thomas Jefferson UniversityLeonard G Gomella - Thomas Jefferson UniversityLucia R Languino - Thomas Jefferson UniversityRichard G Pestell - Thomas Jefferson University
- Publication Details
- Cancer research (Chicago, Ill.), v 76(22), pp 6723-6734
- Publisher
- American Association for Cancer Research (AACR)
- Grant note
- R01 CA132115 / NCI NIH HHS R01 CA109874 / NCI NIH HHS R01 CA075503 / NCI NIH HHS P30 CA051008 / NCI NIH HHS R01 CA086072 / NCI NIH HHS R01 CA107382 / NCI NIH HHS R01 CA070896 / NCI NIH HHS P30 CA056036 / NCI NIH HHS R00 CA184397 / NCI NIH HHS R03 CA230819 / NCI NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology; School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000388742100029
- Scopus ID
- 2-s2.0-84995467881
- Other Identifier
- 991019168167704721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Oncology