Kun-Chun Chiang1, Shu-Yuan Hsu2, Sheng-Jia Lin3, Chun-Nan Yeh4, Jong-Hwei S Pang5, Shang-Yu Wang4, Jun-Te Hsu4, Ta-Sen Yeh4, Li-Wei Chen6, Sheng-Fong Kuo7, Yi-Chuan Cheng8, Horng-Heng Juang9. 1. General Surgery Department, Chang Gung University, Chang Gung Memorial Hospital, Keelung, Taiwan, R.O.C. Zebrafish Center of Keelung Chang Gung Memorial Hospital, Keelung, Taiwan, R.O.C. 2. Department of Anatomy, College of Medicine, Chang Gung University, Taoyuan, Taiwan, R.O.C. 3. Graduate Institute of Biomedical Sciences, College of Medicine, Chang-Gung University, Taoyuan, Taiwan, R.O.C. 4. Department of General Surgery, Chang Gung University, Chang Gung Memorial Hospital, Taoyuan, Taiwan, R.O.C. 5. Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan, R.O.C. 6. Department of Gastroenterology, Chang Gung University, Chang Gung Memorial Hospital, Keelung, Taiwan, R.O.C. 7. Department of Endocrinology and Metabolism, Chang Gung University, Chang Gung Memorial Hospital, Keelung, Taiwan, R.O.C. 8. Graduate Institute of Biomedical Sciences, College of Medicine, Chang-Gung University, Taoyuan, Taiwan, R.O.C. yccheng@mail.cgu.edu.tw hhj143@mail.cgu.edu.tw. 9. Department of Anatomy, College of Medicine, Chang Gung University, Taoyuan, Taiwan, R.O.C. Department of Urology, Chang Gung University, Chang Gung Memorial Hospital, Taoyuan, Taiwan, R.O.C. yccheng@mail.cgu.edu.tw hhj143@mail.cgu.edu.tw.
Abstract
BACKGROUND/AIM: Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) insufficiency is commonly found in breast cancer patients with metastasis. We investigated the mechanisms by which PTEN affects breast cancer metastatic behavior. MATERIALS AND METHODS: Migration and invasion assay, western blot, immunofluorescent staining and zebrafish animal model were applied. RESULTS: We showed that PTEN insufficiency induced an increase in MCF-7 cell migration and invasion through induction of epithelial-mesenchymal transition (EMT), which was triggered by up-regulation of the EMT-inducing transcriptional factors Zeb1, Zeb2, Snail, Slug and Twist. Simultaneously, E-cadherin expression was inhibited and P-cadherin was up-regulated. Further, WNT1 inducible signaling pathway protein 1 (WISP1) and lipocalin-2 (LCN2) expressions were increased after PTEN knockdown in MCF-7 cells, which also exhibited increased filamentous actin (F-actin) synthesis and extracellular matrix metalloproteinase-2 (MMP-2) and MMP-9 expression. We further showed that PTEN knockdown in MCF-7 cells could increase cell migration in the xenograft zebrafish model. CONCLUSION: Our findings reveal new therapeutic targets for breast cancer patients with PTEN insufficiency. Copyright
BACKGROUND/AIM: Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) insufficiency is commonly found in breast cancerpatients with metastasis. We investigated the mechanisms by which PTEN affects breast cancer metastatic behavior. MATERIALS AND METHODS: Migration and invasion assay, western blot, immunofluorescent staining and zebrafish animal model were applied. RESULTS: We showed that PTEN insufficiency induced an increase in MCF-7 cell migration and invasion through induction of epithelial-mesenchymal transition (EMT), which was triggered by up-regulation of the EMT-inducing transcriptional factors Zeb1, Zeb2, Snail, Slug and Twist. Simultaneously, E-cadherin expression was inhibited and P-cadherin was up-regulated. Further, WNT1 inducible signaling pathway protein 1 (WISP1) and lipocalin-2 (LCN2) expressions were increased after PTEN knockdown in MCF-7 cells, which also exhibited increased filamentous actin (F-actin) synthesis and extracellular matrix metalloproteinase-2 (MMP-2) and MMP-9 expression. We further showed that PTEN knockdown in MCF-7 cells could increase cell migration in the xenograft zebrafish model. CONCLUSION: Our findings reveal new therapeutic targets for breast cancerpatients with PTEN insufficiency. Copyright
Authors: Ida Ayu Ika Wahyuniari; I Gusti Kamasan Nyoman Arijana; Ni Putu Sriwidyani; Hery Suwito; Sitarina Widyarini; Muhammad Ghufron; Mustofa Mustofa; Sofia Mubarika Haryana Journal: Asian Pac J Cancer Prev Date: 2020-05-01