聯絡電話
彭瑞銘
副教授
細胞力學與訊息傳遞
腫瘤生物學與微環境
癌症生物標記與治療
- 電子郵件信箱
r.jmpeng@gmail.com
研究簡介
VIM 促進腫瘤的 EMT-MET 轉化和細胞轉移
上皮間質轉化 (EMT) 過程是惡性腫瘤發生的重要原因，腫瘤微環境在誘導 EMT 過程中具有重要的作用。在形態發育的過程中，EMT 最初是指上皮细胞轉化為具轉移能力的细胞。後來用來描述癌細胞在癌症進展和轉移過程中的轉化現象。其主要的訊息傳遞路徑包括 TGF-β、Wnt、Notch、生長因子接受體、發炎因子和缺氧等，其中 TGF-β 調控路徑被認為是 EMT 發生的主要原因。癌細胞通常在發生 EMT 過程後轉移，在新的環境中形成第二個聚落。因此，EMT 過程在腫瘤轉移中有著促進的作用。目前已知，腫瘤在其侵襲性細胞的前端將通過 EMT 轉化為間質型細胞，使其轉移到周圍組織或血管內。然而，這些在前端具侵襲性的細胞透過 EMT 訊息傳遞路徑來影響細胞骨架重組的機制尚未清楚。因此，了解 EMT 過程在這些侵襲性細胞中的作用機制將有利於藥物開發。
Vimentin (VIM) 異常增加是癌症惡化的重要指標之一。VIM 是一種中間絲蛋白，是細胞骨架蛋白的成員之一，在 EMT 過程中，VIM 在細胞從貼附轉變成移動的過程中扮演著關鍵作用。目前，VIM 的表達量可能是胃癌患者預後不良的指標之一，但在其他腫瘤的臨床病理特徵及預後仍然存在爭議。因此，探討 VIM 在 EMT 進展中的功能及其機制，可以為臨床癌症診斷提供更清楚的定義。
VIM 調控肌動蛋白應力纖維的形成和侵襲性前導細胞的細胞貼附
肌動蛋白的結構和黏附蛋白 (focal adhesion proteins) 的排列與細胞轉移有關，利用創傷癒合實驗，我們發現對照組細胞存在大量的肌動蛋白應力纖維及黏附蛋白 (Vinculin) 在細胞內部，使前導細胞運動逐漸變慢。而 VIM 的缺失會大幅減少肌動蛋白的應力纖維形成，並導致 Vinculin 移位到細胞膜週邊，這有助於細胞快速前進。在前導細胞缺乏 VIM 的情況下，細胞內含較少的肌動蛋白應力纖維和較多的 vinculin 在細胞膜附近，進而大幅促進細胞的移動。
在創傷癒合實驗過程中，前導細胞會產生逐漸產生大量的細胞內肌動蛋白應力纖維，而 VIM 的缺失使肌動蛋白應力纖維明顯減少。在細胞移動過程中隨著肌動蛋白形成細絲，VIM 的表現也會逐漸增加，並促進肌動蛋白絲結合形成纖維束而產生強有力的結構。TGF-β 的刺激會促進 VIM 的表現，而抑制 TGF-B 可以減少 VIM 的產生。在免疫細胞辨識和攻擊癌細胞的過程中，阻斷 TGF-β 的作用會協同增强抗 PD-L1 抗體促進免疫細胞浸潤的治療效果，因而 EMT-MET 轉化過程在免疫細胞運作時亦扮演重要的影響，探討其作用機制將有助於腫瘤免疫治療的應用。
學術著作
Recent publications (Pubmed Search)
1: Hsu CC, Wu KLH, Peng JM, Wu YN, Chen HT, Lee MS, Cheng JH. Low-energy
extracorporeal shockwave therapy improves locomotor functions, tissue
regeneration, and modulating the inflammation induced FGF1 and FGF2 signaling to
protect damaged tissue in spinal cord injury of rat model: an experimental
animal study. Int J Surg. 2024 Dec 1;110(12):7563-7572. doi:
10.1097/JS9.0000000000002128. PMID: 39453843; PMCID: PMC11634128.
2: Peng JM, Su YL. Lymph node metastasis and tumor-educated immune tolerance:
Potential therapeutic targets against distant metastasis. Biochem Pharmacol.
2023 Sep;215:115731. doi: 10.1016/j.bcp.2023.115731. Epub 2023 Aug 2. PMID:
37541450.
3: Su YL, Xiao LY, Huang SY, Wu CC, Chang LC, Chen YH, Luo HL, Huang CC, Liu TT,
Peng JM. Inhibiting WEE1 Augments the Antitumor Efficacy of Cisplatin in
Urothelial Carcinoma by Enhancing the DNA Damage Process. Cells. 2023 May
25;12(11):1471. doi: 10.3390/cells12111471. PMID: 37296592; PMCID: PMC10252844.
4: Luo HL, Chang YL, Liu HY, Wu YT, Sung MT, Su YL, Huang CC, Wang PC, Peng JM.
VCAN Hypomethylation and Expression as Predictive Biomarkers of Drug Sensitivity
in Upper Urinary Tract Urothelial Carcinoma. Int J Mol Sci. 2023 Apr
19;24(8):7486. doi: 10.3390/ijms24087486. PMID: 37108649; PMCID: PMC10139123.
5: Peng JM, Chiu CF, Cheng JH, Liu HY, Chang YL, Luo JW, Weng YT, Luo HL.
Evasion of NK cell immune surveillance via the vimentin-mediated
cytoskeleton remodeling. Front Immunol. 2022 Aug 11;13:883178. doi:
10.3389/fimmu.2022.883178. PMID: 36032170; PMCID: PMC9402923.
6: Park JM, Peng JM, Shen YS, Lin CY, Hsu TW, Su YH, Chen HA, Saengboonmee C,
Chang JS, Chiu CF, Shan YS. Phosphomimetic Dicer S1016E triggers a switch to
glutamine metabolism in gemcitabine-resistant pancreatic cancer. Mol Metab. 2022
Nov;65:101576. doi: 10.1016/j.molmet.2022.101576. Epub 2022 Aug 19. PMID:
35995401; PMCID: PMC9460536.
7: Cheng JH, Chou WY, Wang CJ, Siu KK, Peng JM, Wu YN, Lee MS, Huang CY, Ko JY,
Jhan SW. Pathological, Morphometric and Correlation Analysis of the Modified
Mankin Score, Tidemark Roughness and Calcified Cartilage Thickness in Rat Knee
Osteoarthritis after Extracorporeal Shockwave Therapy. Int J Med Sci. 2022 Jan
1;19(2):242-256. doi: 10.7150/ijms.67741. PMID: 35165510; PMCID: PMC8795810.
8: Peng JM, Chen WY, Cheng JH, Luo JW, Tzeng HT. Dysregulation of Cytoskeleton
Remodeling Drives Invasive Leading Cells Detachment. Cancers (Basel). 2021 Nov
11;13(22):5648. doi: 10.3390/cancers13225648. PMID: 34830801; PMCID: PMC8616115.
9: Luo HL, Liu HY, Chang YL, Sung MT, Chen PY, Su YL, Huang CC, Peng JM.
Hypomethylated RRBP1 Potentiates Tumor Malignancy and Chemoresistance in Upper
Tract Urothelial Carcinoma. Int J Mol Sci. 2021 Aug 16;22(16):8761. doi:
10.3390/ijms22168761. PMID: 34445467; PMCID: PMC8395942.
10: Peng JM, Hsieh SY, Cheng JH, Luo JW, Su YL, Luo HL. Confirming whether
KLHL23 deficiency potentiates migration in urothelial carcinoma. Chin J Physiol.
2021 May-Jun;64(3):142-149. doi: 10.4103/cjp.cjp_110_20. PMID: 34169920.
11: Peng JM, Lin SH, Yu MC, Hsieh SY. CLIC1 recruits PIP5K1A/C to induce cell-
matrix adhesions for tumor metastasis. J Clin Invest. 2021 Jan 4;131(1):e133525.
doi: 10.1172/JCI133525. PMID: 33079727; PMCID: PMC7773349.
12: Peng JM, Tseng RH, Shih TC, Hsieh SY. CAMK2N1 suppresses hepatoma growth
through inhibiting E2F1-mediated cell-cycle signaling. Cancer Lett. 2021 Jan
28;497:66-76. doi: 10.1016/j.canlet.2020.10.017. Epub 2020 Oct 15. PMID:
33068700.
13: Peng JM, Bera R, Chiou CY, Yu MC, Chen TC, Chen CW, Wang TR, Chiang WL, Chai
SP, Wei Y, Wang H, Hung MC, Hsieh SY. Actin cytoskeleton remodeling drives
epithelial-mesenchymal transition for hepatoma invasion and metastasis in mice.
Hepatology. 2018 Jun;67(6):2226-2243. doi: 10.1002/hep.29678. Epub 2018 Apr 19.
PMID: 29171033.
14: Bera R, Chiou CY, Yu MC, Peng JM, He CR, Hsu CY, Huang HL, Ho UY, Lin SM,
Lin YJ, Hsieh SY. Functional genomics identified a novel protein tyrosine
phosphatase receptor type F-mediated growth inhibition in hepatocarcinogenesis.
Hepatology. 2014 Jun;59(6):2238-50. doi: 10.1002/hep.27030. Epub 2014 Apr 25.
PMID: 24470239.
15: Chiu CF, Peng JM, Hung SW, Liang CM, Liang SM. Recombinant viral capsid
protein VP1 suppresses migration and invasion of human cervical cancer by
modulating phosphorylated prohibitin in lipid rafts. Cancer Lett. 2012 Jul
28;320(2):205-14. doi: 10.1016/j.canlet.2012.02.027. Epub 2012 Mar 3. PMID:
22388104.
16: Peng JM, Chen YH, Hung SW, Chiu CF, Ho MY, Lee YJ, Lai TC, Hsiao M, Liang
CM, Liang SM. Recombinant viral protein promotes apoptosis and suppresses
invasion of ovarian adenocarcinoma cells by targeting α5β1 integrin to down-
regulate Akt and MMP-2. Br J Pharmacol. 2012 Jan;165(2):479-93. doi:
10.1111/j.1476-5381.2011.01581.x. PMID: 21740408; PMCID: PMC3268200.
17: Huang CY, Liang CM, Chu CL, Peng JM, Liang SM. A fibrillar form of
fibronectin induces apoptosis by activating SHP-2 and stress fiber formation.
Apoptosis. 2010 Aug;15(8):915-26. doi: 10.1007/s10495-010-0500-1. PMID:
20414729.
18: Peng JM, Liang SM, Liang CM. VP1 of foot-and-mouth disease virus induces
apoptosis via the Akt signaling pathway. J Biol Chem. 2004 Dec
10;279(50):52168-74. doi: 10.1074/jbc.M403686200. Epub 2004 Oct 5. PMID:
15466859.
19: Wang JH, Liang CM, Peng JM, Shieh JJ, Jong MH, Lin YL, Sieber M, Liang SM.
Induction of immunity in swine by purified recombinant VP1 of foot-and-mouth
disease virus. Vaccine. 2003 Sep 8;21(25-26):3721-9. doi:
10.1016/s0264-410x(03)00363-3. PMID: 12922103.
研究團隊
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羅佳紋研究助理
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學術履歷
EDUCATION:
2004 – 2011 Ph.D.
Institute of Biochemical Sciences,
National Taiwan University, Taiwan
1998 – 2000 M.S.
Institute of Microbiology,
National Taiwan University, Taiwan
PROFESSIONAL EXPERIENCE:
2018/8 ~ present Assistant Professor
Institute for Translational Research in Biomedicine,
Kaohsiung Chang Gung Memorial Hospital,
Kaohsiung, Taiwan
2012/5 ~ 2018/7 Postdoctoral Research Fellow
Liver Research Unit,
Chang Gung Memorial Hospital, Linko, Taiwan
AWARDS:
2009 The award of excellent poster, the 24th Joint Annual Conference of Biomedical Sciences, The Taiwan Society of Biochemistry and Molecular Biology.
2006 Best student in the Ph.D. poster competition, Institute of Biochemical Sciences, National Taiwan University, Taiwan.
2005 The award of outstanding research, Institute of Biochemical Sciences, National Taiwan University, Taiwan.
2004 The award of outstanding research, Jung-Yaw Lin Foundation, Taiwan.
RESEARCH INTERESTS:
• Molecular mechanisms of cell cytoskeleton
• Discovery of cancer biomarkers
• Tumor microenvironment
• Prevention and therapy of cancer: preclinical study
PUBLICATION LIST:
1. Peng JM, Bera R, Chiou CY, Yu MC, Chen TC, Chen CW, Wang TR, Chiang WL, Chai SP, Wei Y, Wang H, Hung MC, Hsieh SY. Actin cytoskeleton remodeling drives epithelial-mesenchymal transition for hepatoma invasion and metastasis in mice. Hepatology, 67(6): 2226-2243 (2018)
2. Bera R, Chiou CY, Yu MC, Peng JM, He CR, Hsu CY, Huang HL, Ho UY, Lin SM, Lin YJ, Hsieh SY. Functional genomics identified a novel protein tyrosine phosphatase receptor type F-mediated growth inhibition in hepatocarcinogenesis. Hepatology, 59(6): 2238-2250 (2014)
3. Chiu CF, Ho MY, Peng JM, Hung SW, Lee WH, Liang CM, Liang SM. Raf activation by Ras and promotion of cellular metastasis require phosphorylation of prohibitin in the raft domain of the plasma membrane. Oncogene, 32(6): 777-787 (2013)
4. Peng JM, Chen YH, Hung SW, Chiu CF, Ho MY, Lee YJ, Lai TC, Hsiao M, Liang CM, Liang SM. Recombinant viral protein promotes apoptosis and suppresses invasion of ovarian adenocarcinoma cells by targeting alpha5beta1 integrin to down-regulate Akt and MMP-2. British Journal of Pharmacology, 165(2): 479-493 (2012)
5. Chiu CF, Peng JM, Hung SW, Liang CM, Liang SM. Recombinant viral capsid protein VP1 suppresses migration and invasion of human cervical cancer by modulating phosphorylated prohibitin in lipid rafts. Cancer letters, 320(2): 205-214 (2012)
6. Huang CY, Liang CM, Chu CL, Peng JM, Liang SM. A fibrillar form of fibronectin induces apoptosis by activating SHP-2 and stress fiber formation. Apoptosis, 15(8): 915-926 (2010)
7. Peng JM, Liang SM, Liang CM. VP1 of foot-and-mouth disease virus induces apoptosis via the Akt signaling pathway. Journal of Biological Chemistry, 279(50): 52168-52174 (2004)
8. Wang JH, Liang CM, Peng JM, Shieh JJ, Jong MH, Lin YL, Sieber M, Liang SM. Induction of immunity in swine by purified recombinant VP1 of foot-and-mouth disease virus. Vaccine, 21(25-26): 3721-3729 (2003)
9. Lin YC, Peng JM, Wang WB. The N-terminal common domain of simian virus 40 large T and small t antigens acts as a transformation suppressor of the HER-2/neu oncogene. Oncogene, 19(22): 2704-2713 (2000)