The Role of Gut-Enriched Krüppel-Like Factor (GKLF)/ KLF4 in Gastrointestinal Tract-Related Cancers

GKLF/ KLF4 在消化道相關癌症中所扮演的角色

許蕙子(Hui-Tzu Hsu) ； 宋明達(Ming-Ta Sung) ； 李直隽(Chih-Chun Lee) ； 張玉芳(Yuh-Fang Chang) ； 戚謹文(Chin-Wen Chi)

《台灣癌症醫學雜誌》 27卷5期 (2011/10) Pp. 191-199

https://doi.org/10.6323/JoCRP.2011.27.5.1

摘要

GKLF亦稱為KLF4是一種具有鋅手指結構的轉錄因子，於腸道的上皮層有高度的表現量，在正常的組織中扮演了調控細胞生長、分化、發育以及死亡。KLF4在不同的癌症中扮演不同的角色，可能是扮演抑制也可能是促進癌症發展的角色。研究結果指出，當過度表現KLF4 時癌細胞的生長會降低，其作用機轉可能是透過降低細胞生長的細胞週期蛋蛋白cyclin D1表現量，並且增加細胞週期蛋白依賴性激酶抑制蛋白，p21的表現量，使得生長受到抑制。相反地，當降低KLF4 表現量時，則會恢復癌細胞的生長。此外，體外研究結果指出於乳腺上皮細胞和乳癌細胞中KLF4 會透過增加E-cadherin的表現量抑制表皮-間質轉換。而在臨床消化道癌症包括食道癌、胃癌、肝癌、胰臟癌以及大腸癌都發現到有較低的KLF4表現量。然而，在口腔癌以及乳癌中卻發現KLF4 的表現量增加，並且扮演了促進癌症發展的角色。回顧相關研究結果均指出，檢測癌細胞中KLF4的表現量高低有助於瞭解在癌症發展過程中KLF4所扮演的角色，並且有可能作為診斷上的一個標的以助於在消化道相關癌症的治療。

關鍵字

表皮-間質轉換 ； Krüppel樣因子4 ； 細胞週期蛋白D1 ； p21

並列摘要

Gut-enriched Krüppel-like factor (GKLF), also called KLF4, is a zinc finger transcription factor, highly expressed in the epithelium and regulates cell proliferation, differentiation, development and apoptosis. KLF4 plays diverse roles in different cancers, functioning as a tumor suppressor or an oncogene. It has been shown that overexpression of KLF4 has led to decreased cancer cell growth through down-regulating cyclin D1 and increased p21, resulting in cell cycle arrest and thus acting as a tumor suppressor. Conversely, the knockdown of KLF4 expression restored cancer cell growth. In addition, KLF4 up-regulates E-cadherin expression to inhibit epithelial- mesenchymal transition (EMT) in mammary epithelial cells and breast cancer cells in vitro. Recently, many studies have revealed that a lower expression of KLF4 was observed in gastrointestinal tract-related tumors, including esophageal squamous cancer, gastric cancer, hepatocellular carcimona (HCC), ductal pancreatic carcinoma and colon cancer. In contrast, increased KLF4 expression was detected in oral squamous cell carcinoma and ductal carcinoma of the breast, promoting aggressive phenotype as an oncogene. These results indicated KLF4 and related signal transduction pathways have the potential to become diagnostic markers and/or therapeutic targets in gastrointestinal track related cancers.

並列關鍵字

epithelial-mesenchymal transition ； Krüppel-like factor 4 ； cyclin D1 ； p21