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Mesenchymal Phenotypic Switching of Breast Cancer Cells Driven by Intercellular Adhesion Molecule-1 and PIM2 Kinase

Title
Mesenchymal Phenotypic Switching of Breast Cancer Cells Driven by Intercellular Adhesion Molecule-1 and PIM2 Kinase
Other Titles
PIM2 Kinase와 Intercellular Adhesion Molecule1에 의한 유방암세포의 중간엽성 세포형질 획득 기전
Author
니잠우드딘
Advisor(s)
이수재
Issue Date
2017-02
Publisher
한양대학교
Degree
Doctor
Abstract
Breast cancer, which often starts as a local tumor, metastasizes to the lungs, bones and other organs. Therapeutic strategies for breast cancer involve targeting of specific cell membrane receptors which facilitate delivery of the therapeutic agent to the tumor site. Often, basal-like metastatic form of breast tumor has high motility rate due to the aggressive propagation rate, invasiveness and lack of effective available treatments. Due to the lack of commonly targeted cell surface receptors like human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER) and progesterone receptor (PR), targeted therapies cannot discriminate basal-like cancer cells, following difficulty in treatment. Therefore, there is an urgent need to identify new molecular markers and signaling nodes for the effective treatment of basal-like breast cancer cells. In this dissertation, I attempted to understand the mechanisms involved in the invasiveness of breast cancer. Importantly, I found that ICAM1 and PIM2 have a critical role in enhancing malignant phenotype of basal-like breast cancer. ICAM1 is highly expressed in invasive basal-like breast cancer thereby activating EGFR, where it promotes Epithelial to Mesenchymal Transition (EMT) through the activation of JAK1/STAT3 signaling node. Also, PIM2 kinase was found to induce the activation of STAT3 in breast cancer through the secretion of cytokines IL-1α and IL-8, which form a feedback loop with STAT3 to regulate the expression of PIM2. Collectively, in this dissertation, it is proposed that targeting ICAM1 and PIM2 can be beneficial adjuvant therapy for the treatment of malignant form of breast cancer.
URI
https://repository.hanyang.ac.kr/handle/20.500.11754/124920http://hanyang.dcollection.net/common/orgView/200000429672
Appears in Collections:
GRADUATE SCHOOL[S](대학원) > DEPARTMENT OF MOLECULAR AND ENVIRONMENTAL BIOSCIENCE(분자생명환경과학과) > Theses (Ph.D.)
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