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Targeting ILK to Eliminate IL-6 Induced Cancer Stem Cell Phenotype
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| 자료유형 | 학위논문 |
|---|---|
| 서명/저자사항 | Targeting ILK to Eliminate IL-6 Induced Cancer Stem Cell Phenotype. |
| 개인저자 | Hsu, En-Chi. |
| 단체저자명 | The Ohio State University. Pharmacy. |
| 발행사항 | [S.l.]: The Ohio State University., 2014. |
| 발행사항 | Ann Arbor: ProQuest Dissertations & Theses, 2014. |
| 형태사항 | 138 p. |
| 기본자료 저록 | Dissertations Abstracts International 81-06B. Dissertation Abstract International |
| ISBN | 9781687976970 |
| 학위논문주기 | Thesis (Ph.D.)--The Ohio State University, 2014. |
| 일반주기 |
Source: Dissertations Abstracts International, Volume: 81-06, Section: B.
Advisor: Chen, Ching-Shih. |
| 이용제한사항 | This item must not be sold to any third party vendors. |
| 요약 | Cancer stem cell (CSC) has been associated with the aggressive phenotype of cancer, including potent cancer initiation, drug resistance and metastasis. Triple negative breast cancer (TNBC), a breast cancer subtype with aggressive behavior and no effective targeting therapy, has been shown correlations with autocrine interleukin-6 (IL-6) dependent survival and increasing CSC population. The inflammatory cytokine IL-6 induces CSC by activating STAT3 and NF-觀B pathway. Integrin-linked kinase (ILK), which links cell-adhesion receptors, integrins and growth factors to the actin cytoskeleton and regulates multiple signaling pathways such as Akt, AP-1 and NF-觀B pathways, is highly expressed in various cancers. In breast cancer cell lines, we showed that ILK expression is tightly associated with IL-6 expression and Notch1 activation, which is important for maintaining the self-renewal capacity of CSC. The objective of this study is to characterize the regulatory interactions among IL-6, ILK, and Notch1 in breast CSC. Our work shows that IL-6 upregulated ILK expression via E2F1 which, in turn, amplified the IL-6-NF-觀B positive signaling loop and stimulated downstream Notch1 activation. We also identified a novel role for ILK in the maturation of gamma-secretase, which cleaves and activates Notch 1. Immunohistochemical staining of a human breast tumor tissue microarray revealed a positive correlation between ILK and IL-6 expression. Moreover, high ILK expression showed low relapse-free survival probability (P = 0.045) among subgroup of patients with high IL-6 expression. These data indicate an integral role of ILK in IL-6-mediated signaling and consequent induction in CSC |
| 일반주제명 | Biochemistry. Biomedical engineering. Molecular biology. Pharmaceutical sciences. Physiology. Epidemiology. Public health. Oncology. Health sciences. |
| 언어 | 영어 |
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