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Kuo-Chu Lai

                       

Kuo-Chu Lai

Appointments：Associate Professor

Lab：Cell Cytotoxicity Laboratory

Education：Ph.D.

School/Nation：National Yang Ming Chiao Tung  University/Taiwan

Tel: #3035

E-mail: kuochu@mail.cgu.edu.tw

Research website: https://tcue504.weebly.com/

研究室現有： 博士後研究員  人

博士班研究生    人

碩士班研究生 2 人

專任研究助理   1 人

大學部專題生    人

Research outline：(1-3 pages)

My major research interests are exploring the underlying mechanism of cancer cachexia and developing effective therapeutic agents against cancer growth and progression. Our studies will provide new insight into the cancer cachexia and potential strategies for cancer treatment.

  1. Investigation of the molecular mechanism of cancer metastasis and cachexia

Head and neck cancer (HNC) is the sixth most common cancer in the world. There are 600,000 new cases of HNC are diagnosed worldwide each year each year. Epidemiological studies over last 20 years reveal that the overall incidence of young patients under 45 who encounter HNC, especially oral squamous cell carcinoma (OSCC), is growing steadily. Therefore, understanding the molecular mechanism of HNC progression is the basis for developing therapeutic strategies. Our preliminary results have demonstrated that interferon induced protein with tetratricopeptide repeats 2 (IFIT2) depletion could enhance epithelial-mesenchymal transition (EMT), migration, invasion, angiogenesis, and metastasis, suggesting that IFIT2 may act as a metastasis suppressor. More currently, we found that mice bearing HNC cells expressing sh-IFIT2 exhibited cachexia syndrome. Cachexia syndrome is one of the most lethal effects in cancer patients. The frequency of cancer-related cachexia is considerably high (60-80%) in HNC. However, the detail mechanisms responsible for cancer cachexia are poorly understood. Therefore, we aim to investigate the role of IFIT2 in HNC cachexia..

II. Discovery and development of anticancer agents from natural products or novel synthetic chemicals

In the past, we have made efforts to examine the anti-tumor effects of natural products, such as oroxylin A, Antrodia cinnamomea (AC) and novel synthetic quinazolinone derivatives. To mimic the chronic use of natural products, we established an in vitro long-term treatment model and demonstrated that oroxylin A inhibition of migration following long-term treatment may be due to its suppression of CCL2 in OSCC cells. Moreover, we explored the antitumor effect of novel Antrodia cinnamomea extract on colorectal cancer cells. We are currently focusing on the anti-tumor effects of novel DNA bifunctional alkylating agents and quinazoline derivations. In the future, more natural products or novel synthetic chemicals will be tested.

Publications:

  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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