title: Tripartite motif 16 suppresses breast cancer stem cell properties through regulation of Gli-1 degradation via the ubiquitin-proteasome pathway.
abstract: Cancer stem cells (CSCs) are responsible for cancer progression and patient prognosis. Tripartite motif 16 (TRIM16) is a proteasome coactivator that regulates proteolytic activity in eukaryotic cells. Abundant evidence has shown that TRIM16 is lowly expressed in a number of human carcinomas. In a previous study, we demonstrated that TRIM16 suppressed cancer malignancy and that TRIM16 expression levels were associated with favorable prognostic parameters of patients with cancer. However, the precise role of this motif in the pathogenesis of breast cancer remains unknown. In the present study, we examined 29 human breast cancer specimens, and found that TRIM16 was lowly expressed in breast cancers; thus, TRIM16 expression is negatively correlated with metastasis in breast cancer patients. Moreover, we showed that TRIM16 suppressed CSC properties in a population of breast cancer cells. TRIM16 depletion resulted in an increased proportion of CSCs relative to breast cancer cells when several assays were used to assess CSC properties. Finally, we demonstrated that TRIM16 directly regulated the degradation of Gli‑1 protein via the ubiquitin‑proteasome pathway. In conclusion, we propose that inhibition of CSC properties may be one of the functions of TRIM16 as a suppressor of breast cancer progression.
authors.affiliation: The Integrated Department of TCM and Western Medicine, Shaanxi Provincial Tumor Hospital, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Juntao
authors.initials: J
authors.lastname: Yao
authors.affiliation: Department of Thoracic Surgery, The Center Hospital of Xi'an, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Xu
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Tian
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Fu
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Oncology, Shaanxi Provincial Tumor Hospital, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Suoni
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Shi
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Aili
authors.initials: A
authors.lastname: Suo
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Ruan
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yao
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000737:chemistry / Q000473:pathology*; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000235:genetics / Q000502:physiology*; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D059748:Proteolysis; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D011994:Recombinant Proteins / Q000378:metabolism; D018874:Spheroids, Cellular; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D014162:Transfection; D000070584:Tripartite Motif Proteins; D025801:Ubiquitin / Q000502:physiology; D044767:Ubiquitin-Protein Ligases; D054875:Ubiquitination; D000071676:Zinc Finger Protein GLI1
chemical_list: D004268:DNA-Binding Proteins; C400551:GLI1 protein, human; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D014157:Transcription Factors; D000070584:Tripartite Motif Proteins; D025801:Ubiquitin; D000071676:Zinc Finger Protein GLI1; C117731:TRIM16 protein, human; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex