研究方向及研究室特色：

本研究室的主要方向為探索癌症轉移及惡病質的分子機制，並開發有效對抗腫瘤生長和進展的天然物或新型合成藥物。研究成果將為癌症轉移、惡病質分子機轉和癌症治療策略提供新見解。

1. 探討癌症轉移/惡病質的分子機制

頭頸癌是世界第六大最常見的癌症。每年全球每年有60萬新診斷的頭頸癌病例。過去20年流行病學研究表明， 45歲以下年輕頭頸癌患者（尤其是口腔鱗狀細胞癌）的整體發生率正在穩定增長。因此，瞭解頭頸癌進展的分子機轉是開發治療策略的基礎。我們過去研究顯示頭頸癌細胞中IFIT2 (interferon induced protein with tetratricopeptide repeats 2) 蛋白缺失可以增強上皮-間質轉化（epithelial-mesenchymal transition），遷移 (migration)，侵襲 (invasion)，血管生成 (angiogenesis) 和轉移 (metastasis)，闡明IFIT2抑制癌症轉移之作用。近來實驗結果發現轉移性IFIT2蛋白缺失頭頸癌腫瘤會造成小鼠表現惡病質症狀。惡病質是癌症患者中最致命的影響之一。頭頸癌病患中發生惡病質的頻率相當高（60-80％）。然而，其詳細分子機制了解甚少。因此，我們未來目標為探究頭頸癌症轉移、惡病質的分子機轉。

2. 開發具有抗腫瘤潛力的天然產物或新型合成藥物

過去，我們也測試天然物，如木蝴蝶素A (oroxylin A)、牛樟芝 (Antrodia cinnamomea; AC) 萃取物，及新合成喹唑啉酮衍生物 (quinazolinone derivatives) 對抗腫瘤的治療潛力。為了檢測天然物長期服用的抗腫瘤潛力，我們建立了體外長期暴露模型並證明了長期木蝴蝶素A暴露可抑制口腔癌細胞中CCL2訊息傳遞路徑進而削減癌細胞的遷移。此外，亦證實新型牛樟芝萃取物在結腸直腸癌細胞的抗腫瘤機制。目前則是檢測新型DNA雙功能烷基化劑和新型喹唑啉衍生物之抗腫瘤作用。未來將會試驗更多對腫瘤生長和進展有治療潛力的天然物或新型合成化學製劑。

論文發表：

1. Lai KC*, Hong ZX, Hsieh JG, Lee HJ, Yang MH, Hsieh CH, Yang CH, Chen YR. IFIT2-depleted metastatic oral squamous cell carcinoma cells induce muscle atrophy and cancer cachexia in mice. Journal of Cachexia, Sarcopenia and Muscle. Feb., 2022;Journal of Cachexia, Sarcopenia and Muscle 2022; 13: 1314–1328
2. Lai KC, Chia YT, Yih LH, Lu YL, Chang ST, Hong ZX, Chen TL, Hour MJ. Antitumor effects of the novel quinazolinone Holu-12: Induction of mitotic arrest and apoptosis in human oral squamous cell carcinoma CAL27 cells. Anticancer Research. Jan., 2021, 41 (1): 259-268. 
3. Regmi P, Lai KC, Liu CJ, Lee TC. SAHA overcomes 5-FU resistance in IFIT2-depleted oral squamous cell carcinoma cells. Cancers (Basel). Nov., 2020, 12 (12): 3527.doi: 10.3390/cancers 12123527
4. Patel AS, Jain V, Rao VN, Lin YW, Shah A, Lai KC, Su TL, Lee TC. Design, synthesis and antitumour evaluation of pyrrolo[1,2-f]-phenanthridine and dibenzo[f,h]pyrrolo [1,2-b]isoquinoline derivatives. European Journal of Medicinal Chemistry, Sep., 2020, 202:112516.
5. Lin TJ, Lai KC, Lee AS, Chang CH, Liu CL and Chung CH. Novel antrodia cinnamomea extract reduced cancer stem-like phenotype changes and resensitized KRAS-mutant colorectal cancer via a microRNA-27a pathway. Cancers, Oct.,2019, 11(11): 1657. doi: 10.3390/cancers 11111657
6. Ku WT, Tung JJ, Tony JF Lee, Lai KC*. Long-term exposure to oroxylin A inhibits metastasis by suppressing CCL2 in oral squamous cell carcinoma cells. Cancers (Basel).Mar., 2019, 11 (3): 353. doi: 10.3390/cancers 1103035
7. Chu CH, Chang SC, Wang HH, Yang SH, Lai KC*, Lee TC*. Prognostic values of EPDR1 hypermethylation and its inhibitory function on tumor invasion in colorectal cancer. Cancers (Basel). Oct., 2018, 10 (10): 393 doi: 10.3390/cancers 10100393
8. Lai KC, Liu CJ, Lin TJ, Mar AC, Wang HH, Chen CW, Hong ZX, Lee TC. Blocking TNF-α inhibits angiogenesis and growth of IFIT2-depleted metastatic oral squamous cell carcinoma cells. Cancer Letters. Jan., 2016, 370 (2): 207-215.
9. Chen YJ, Lai KC, Kuo HH, Chow LP, Yih LH, Lee TC. HSP70 colocalizes with PLK1 at the centrosome and disturbs spindle dynamics in cells arrested in mitosis by arsenic trioxide. Archives of Toxicology, Sep., 2014, 88 (9):1711-1723.
10. Lai KC, Liu CJ, Chang CK, Lee TC. Depleting IFIT2 mediates atypical PKC signaling to enhance the migration and metastatic activity of oral squamous cell carcinoma cells. Oncogene, Aug., 2013, 32 (32): 3686-3697.
11. Hung KF, Lai KC, Liu TY, Liu CJ, Lee TC, Lo JF. Asb6 upregulation by areca nut extracts is associated with betel quid-induced oral carcinogenesis. Oral Oncology,Jun., 2009, 45 (6):543-548.
12. Lai KC, Chang KW, Liu CJ, Kao SY, Lee TC. IFN-induced protein with tetratricopeptide repeats 2 inhibits migration activity and increases survival of oral squamous cell carcinoma. Molecular Cancer Research, Sep., 2008, 6 (9):1431-1439.
13. Lai KC, Lee TC. Genetic damage in cultured human keratinocytes stressed by long-term exposure to areca nut extracts. Mutation Research- Fundamental and Molecular Mechanisms of Mutagenesis, Jul., 2006, 599 (1-2): 66-75.

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2016 榮獲台灣藥理學會『104年度杜聰明博士年輕學者獎』