Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University

Tumor Metastasis and Drug Resistance

In general, two issues including carcinoma in situ and metastatic tumors are the major parts of metastatic studies. However, the impact of the intravascular microenvironment on tumor metastasis is often ignored, leading to the gap of knowledge in understanding of tumor survival and distal metastasis in anchorage-independent microenvironment. According to clinical relevance, we further investigate cytokines including PGE₂, ANGPTL4, and PTX3 that regulate anoikis resistance, metastasis and drug resistance using cell and animal models. The outcomes of these studies can be further associated with cancer treatment and anticancer drug resistance. In addition, the correlation between the effect of ANGPTL4 and PTX3 on COX-2 activation, resulting in promoting tumor metastasis would be clarified. These results can help us to evaluate anti-inflammatory drugs celecoxib and aspirin in the prevention of cancer metastasis.

Metastatic cancer is malignant and obtains drug resistance which makes it the leading cause of cancer-related death. The metastatic cancer cells not only resist to anoikis in the circulation but also avoid immune surveillance. On the other hand, signal molecules such as cytokines, growth factors, and chemokines in the microenvironment can promotes intravasation. However, the mechanism involved in the regulation of metastatic cancer cells to infiltrate and transplant to distal tissues remains unclear.

1. Shieh JM, Chang TW, Wang JH, Liang SP, Kao PL, Chen LY, Yen CJ, Chen, YJ, Chang WC and Chen BK (2023) RNA-binding protein-regulated fibronectin is essential for EGFR-activated metastasis of head and neck squamous cell carcinoma. FASEB J 37, e23206

2. Shen CJ, Chan RH, Lin BW, Li NC, Huang YH, Chang WC and Chen BK (2023) Oleic acid-induced metastasis of KRAS/p53-mutant colorectal cancer relies on concurrent KRAS activation and IL-8 expression bypassing EGFR activation. Theranostics 13, 4650-4666

3. Huang CR, Chang TW, Lee CT, Shen CJ, Chang WC and Chen BK (2021) ARNT deficiency represses pyruvate dehydrogenase kinase 1 to trigger ROS production and melanoma metastasis. Oncogenesis 10,11

4. Wang CC,Chen BK, Chen PH and Chen LC (2020) Hinokitiol induces cell death and inhibits epidermal growth factor-induced cell migration and signaling pathways in human cervical adenocarcinoma. Taiwan J Obstet Gynecol 59, 698-705

5. Muhammad Irham L, Chou WH, Wang YS, Adikusuma W, Sung-Ching Wong H, Aryani Perwitasari D, Huang WC,Chen BK*, Yang HI and Chang WC (2020) Evaluation for the Genetic Association between Store-Operated Calcium Influx Pathway (STIM1 and ORAI1) and Human Hepatocellular Carcinoma in Patients with Chronic Hepatitis B Infection. Biology (Basel) 9, E388 (*: correspondence)

6. Shen CJ, Chang KY, Lin BW, Ling WT, Su CM, Tsai JP, Liao YH, Hung LY, Chang WC and Chen BK (2020) Oleic acid-induced NOX4 is dependent on ANGPTL4 expression to promote human colorectal cancer metastasis. Theranostics 10, 7083-7099

7. Chiang KH, Shieh JM, Shen CJ, Chang TW, Wu PT, Hsu JY, Tsai JP, Chang WC, and Chen BK (2020) EGF-induced COX-2 regulates metastasis of head and neck squamous cell carcinoma through upregulation of ANGPTL4. Cancer Sci 111, 2004-2015

8. Chang CM, Wong HS, Huang CY, Hsu WL, Maio ZF, Chiu SJ, Tsai YT, Chen BK, Wan YY, Wang JY and Chang WC (2019) Functional effects of let-7g expression in colon cancer metastasis. Cancers 11, 489

9. Lu HF, Wong HS, Chen BK, Liao HT, Hsu YW, Ikegawa S, Cho EC, Hung KS and Chang WC (2018) Integrative genomic analysis for the functional roles of ITPKC in bone mineral density. Biosci. Rep. 38 BSR20181481 https://doi.org/10.1042/BSR20181481

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