top of page

TGF-beta Signaling in Cancer Development and Metastasis

  過去的研究致力於研究轉型生長因子(Transforming Growth Factor-beta, TGF-β)的訊息傳導路徑在多種疾病進程中所扮演的角色,包括癌症以及心血管疾病。TGF-β參與許多導致腫瘤發生的生物學過程。包括細胞增殖、細胞外基質分泌、細胞貼附、移動、分化和凋亡等。藉著調節不同的內吞路徑(clathrin-mediated and caveolae-mediated endocytosis),可以影響TGF-β受體在細胞膜表面上分佈的狀況、降解速度並且積極地影響到TGF-β所引發的訊息強度。研究了解內吞作用控制TGF-β活性的機轉將有助於了解了癌症發生的病理機制以及尋找新穎的癌症治療方式。

  另外利用生物化學及活細胞影像的方式研究細胞骨架蛋白(cytoskeletal proteins, ex: myosins and dynamins)是如何影響趨化作用(chemotaxis)及胞吞(Endocytosis)並且研究其中的調控機制。趨化作用以及胞吞作用在多細胞生物中參與了很多關鍵性的生理過程,例如:胚胎發育、免疫反應、以及神經系統的發育與再生。根據研究顯示細胞骨架的重組所造成的細胞運動主要是由肌球蛋白(myosin)以及肌動蛋白(actin)相互配合所完成。之前的研究成果顯示,帶有特殊序列(Pleckstrin Homology domain, 簡稱PH domain)的肌球蛋白會和細胞膜內表面上的phosphatidylinositol (3,4,5)-triphosphate(PIP3)結合,這樣的結合促進細胞骨架蛋白在細胞膜內側聚合形成纖維狀結構並且將細胞膜向外推擠突出形成偽足,進行細胞移動或吞噬的動作。研究趨化作用及胞吞的分子機制將有助於幫助我們了解許多疾病發生的機轉。

  結合之前的研究經驗以及研究成果,目前的研究方向專注於解開細胞骨架蛋白如何藉著調節內吞作用而調控TGF-β的訊息傳遞,並且進一步尋找治療癌症的新穎治療方法。近年與高雄醫學大學以及本校海洋科學院合作發現數種具有生物活性的天然化合物,這些化合物藉著抑制內吞作用來調節TGF-β受體的活性。未來希望與國內藥學相關的研究單位有更密切的合作,尋找更多具有癌症治療潛力的藥物。

The past research has been dedicated to investigating the role of the Transforming Growth Factor-beta (TGF-β) signaling pathway in various disease processes, including cancer and cardiovascular diseases. TGF-β is involved in numerous biological processes leading to tumor formation, such as cell proliferation, extracellular matrix secretion, cell adhesion, migration, differentiation, and apoptosis. By regulating different endocytic pathways (clathrin-mediated and caveolae-mediated endocytosis), the distribution and degradation of TGF-β receptors on the cell membrane can be influenced, actively affecting the intensity of TGF-β-induced signals. Understanding the mechanism by which endocytosis controls TGF-β activity contributes to unraveling the pathological mechanisms of cancer and finding novel cancer treatment approaches.

Additionally, utilizing biochemical and live-cell imaging techniques, the study explores how cytoskeletal proteins (e.g., myosins and dynamins) impact chemotaxis and endocytosis, investigating their regulatory mechanisms. Chemotaxis and endocytosis play crucial roles in various physiological processes in multicellular organisms, such as embryonic development, immune responses, and the development and regeneration of the nervous system. Research indicates that the reorganization of the cell's movement is primarily orchestrated by the coordination between myosin and actin. Previous studies have shown that myosin with a specific sequence (Pleckstrin Homology domain, PH domain) binds to phosphatidylinositol (3,4,5)-triphosphate (PIP3) on the inner surface of the cell membrane, promoting the aggregation of cytoskeletal proteins into fibrous structures and protruding pseudopods for cell movement or engulfment. Understanding the molecular mechanisms of chemotaxis and endocytosis will aid in comprehending the processes underlying many diseases.

Building on previous research experiences and findings, the current research direction focuses on unraveling how cytoskeletal proteins regulate TGF-β signaling by modulating endocytosis, aiming to discover novel therapeutic approaches for cancer treatment. In recent years, collaboration with Kaohsiung Medical University and our own College of Marine Sciences has led to the discovery of several bioactive natural compounds. These compounds regulate the activity of TGF-β receptors by inhibiting endocytosis. In the future, we hope to collaborate more closely with domestic pharmaceutical research units to identify more drugs with potential for cancer treatment.

bottom of page