課程名稱： 論文選讀（下） - 2008 學分數： 1開課系所： 生科四（甲） 上課時間： Tue, 1:40~3:30 PM任課教師： 賴金美老師（ bio2028@mails.fju.edu.tw ）上課地點： ES 508

週次週次 日期日期 課程內容課程內容 週次週次 日期日期 課程內容課程內容

11 22 月月 2626日日 專討課程介紹與評分方式專討課程介紹與評分方式 99 44 月月 2222日日 期中考週（停課）期中考週（停課）

22 33 月月 0404日日 特別演講特別演講（（ ES609ES609）） 1010 44 月月 2929日日 余明泰、譚國斌余明泰、譚國斌

33 33 月月 1111 日日 專討諮詢（不上課）專討諮詢（不上課） 1111 55 月月 0606日日 劉姿瑩、羅珮純劉姿瑩、羅珮純

44 33 月月 1818日日 藍娬娟、吳宜靜藍娬娟、吳宜靜 1212 55 月月 1313日日 黃鈺雲、黃威呈黃鈺雲、黃威呈

55 33 月月 2525日日 唐逸品、黃勝偉唐逸品、黃勝偉 1313 55 月月 2020日日

66 44 月月 0101日日 粱博凱、林亞君粱博凱、林亞君 1414 55 月月 2727日日

77 44 月月 0808日日 尤聰健、酆茂蓉尤聰健、酆茂蓉 1515 66 月月 0303日日 畢業考週畢業考週

88 44 月月 1515日日 許庭毓、郭培群許庭毓、郭培群 1616 66 月月 1010日日 期末考週期末考週

需需撰寫摘要撰寫摘要；摘要需於前一週；摘要需於前一週W5W5 前前交給老師以做修改，並於報交給老師以做修改，並於報告當天發給每位同學。告當天發給每位同學。

口頭報告口頭報告 4040分鐘，同學或老師提問分鐘，同學或老師提問 1010分鐘。分鐘。

由前一週同學負責借用及歸還投影機並擔任該週報告之主持人由前一週同學負責借用及歸還投影機並擔任該週報告之主持人（負責介紹及發問）。（負責介紹及發問）。  評分：評分：Presentation: 60% [Abstract (20%); Presentation & Discussion (40%)]Presentation: 60% [Abstract (20%); Presentation & Discussion (40%)]

Raising question: 15%Raising question: 15%

Final report (modified power point file): 15% Final report (modified power point file): 15%

出席率：出席率： 10%10%（遲到扣分：（遲到扣分： 0.50.5 分分 // 次）次）

Cell migration Cell migration

in 3D ECMin 3D ECM

Review articleReview article

Tumor-cell invasion and Tumor-cell invasion and migration: diversity and migration: diversity and escape mechanismsescape mechanisms Nature Review 2003 (3) 362-374Nature Review 2003 (3) 362-374

Cell migration in 3D ECMCell migration in 3D ECM

Cell migration in 3D ECMCell migration in 3D ECM

Cell migration in 3D ECMCell migration in 3D ECM

Many studies confirm that the multistep model of cell Many studies confirm that the multistep model of cell migration applies to cancer cells. migration applies to cancer cells.

ECM-degrading enzymesECM-degrading enzymes, such as , such as matrix metalloproteinases matrix metalloproteinases (MMPs)(MMPs) are frequently upregulated in tumor cells, and are frequently upregulated in tumor cells, and facilitate migration facilitate migration in vitroin vitro, as well as dissemination and , as well as dissemination and metastasis metastasis in vivoin vivo. .

The overexpression or activation of The overexpression or activation of the Rac, Rho, ROCK or the Rac, Rho, ROCK or MLCK signaling pathwaysMLCK signaling pathways have been correlated with have been correlated with in vitro in vitro tumor cell migrationtumor cell migration, , as well as as well as in vivo in vivo invasion and invasion and progression. progression.

Pharmacological inhibitors that block Pharmacological inhibitors that block integrins, MMPs, ROCK integrins, MMPs, ROCK or MLCK or MLCK are being developed to interfere with cancer-cell are being developed to interfere with cancer-cell invasion.invasion.

Cancer therapeutics designed to target adhesion receptors or Cancer therapeutics designed to target adhesion receptors or proteases have not yet been show to be effective in clinical proteases have not yet been show to be effective in clinical trials. This might be due to the fact that the cancer cell’s trials. This might be due to the fact that the cancer cell’s migration mechanisms can be reprogrammed, allowing it to migration mechanisms can be reprogrammed, allowing it to maintain its invasive properties via morphological and maintain its invasive properties via morphological and functional de-differentiation.functional de-differentiation.

* * Epithelial-Mesenchymal Transition (EMT)Epithelial-Mesenchymal Transition (EMT)

* Intercellular junctional complex* Intercellular junctional complex

apicalapical

basalbasal

Cell-cell adhesionCell-cell adhesion results from results from interaction between interaction between extracellular domains of cadherins from opposing cellsextracellular domains of cadherins from opposing cells to to form a "cell adhesion zipper", which, if extensive, would form a "cell adhesion zipper", which, if extensive, would hold cells together with great strengthhold cells together with great strength

different cell types might engage in different types of interactions

The greater the number of interacting cadherins in a cluster, the greater the strength of adhesion between apposing cells

Embryonic development is characterized by changes in Embryonic development is characterized by changes in gene expression, cell shape, gene expression, cell shape, cell motility, cell adhesioncell motility, cell adhesion,, etc. etc.

MesenchymeMesenchyme (loose, primarily (loose, primarily

nonadhesive cells)nonadhesive cells)

EpitheliumEpithelium (tightly adherent, (tightly adherent,

organized cell layer)organized cell layer)

* * mesenchymal-epithelial transitionmesenchymal-epithelial transition

N-cadherinN-cadherin

Sites of EMT and MET in the emergence and progression of Sites of EMT and MET in the emergence and progression of carcinoma.carcinoma.

Nature, Vol. 2, 442-454Nature, Vol. 2, 442-454

Drivers and mediators of Drivers and mediators of EMT.EMT.Cell, Vol. 118, 277-279Cell, Vol. 118, 277-279

The morphological transition of EMT was accompanied The morphological transition of EMT was accompanied by by scattering and directional migration toward serum factorsscattering and directional migration toward serum factors, , a a gain of mesenchymal cell markers (fibronectin, vimentin, and N-gain of mesenchymal cell markers (fibronectin, vimentin, and N-cadherin), and a loss of epithelial markers (E-cadherin, and cadherin), and a loss of epithelial markers (E-cadherin, and - - and g-catenin).and g-catenin).