Our Funds at Work

Role of ING4 in melanoma tumor growth

Gang Li, MD., British Columbia Cancer Agency, Vancouver, BC.

Malignant melanoma is a life-threatening skin cancer and its incidence in Caucasian populations has increased faster than any other malignancy during the last 20 years. Patients with metastatic melanoma can only survive for 6–8.5 months on average. The molecular mechanism of melanoma pathogenesis is poorly understood. Recently, we found that the expression of ING4, a member of ING (inhibitor of growth) proteins, is significantly reduced in melanoma compared to benign nevi. Furthermore, reduced ING4 expression is closely associated with tumor thickness and tumor ulceration, suggesting that ING4 regulates melanoma cell growth and invasion. Moreover, reduced ING4 expression is significantly correlated with poor patient survival. We are now investigating the molecular mechanisms of ING4 tumor suppressive functions. We will examine how ING4 cooperates with another important tumor suppressor p53 to inhibit melanoma cell migration and if overexpressing ING4 inhibits melanoma tumor growth and metastasis in vivo. This project will not only provide new insights into the molecular mechanisms of ING4 inhibitory effect in melanoma progression, but also test the efficacy of using ING4 as a molecular target for melanoma therapy.

Peer Reviewed Publications Supported by the Canadian Dermatology Foundation

1. Luu Y, Li G. The p53-stabilizing compound CP-31398 does not enhance melanoma chemosensitivity. Anticancer Res. 23: 99-106, 2003
2. Chen B, Campos EI, Crawford R, Martinka M, Li G. Analyses of the tumour suppressor ING1 expression and gene mutation in human basal cell carcinomas. Int. J. Oncol. 22: 927-931, 2003.
3. Ho CK, Bush JA, Li G. Tissue-specific regulation of Apaf-1 expression by p53. Oncol. Reports 10: 1139-1143, 2003.
4. Bush JA, Li G. The role of Bcl-2 family members in the progression of cutaneous melanoma. Clin. Exp. Metastasis 20: 531-539, 2003.
5. Dai D, Makretsov N, Campos EI, Huang C, Zhou Y, Huntsman D, Martinka M, Li, G. Increased expression of integrin-linked kinase is correlated with melanoma progression. Clin. Cancer Res. 9: 4409-4414, 2003. (Highlight article on Journal cover)
6. Chin MY, Li G. Tissue-specific regulation of Chk2 expression by p53. Exp. Mol. Pathol. 75: 131-136, 2003.
7. Su M, Dorocicz I, Dragowska V, Ho V, Li, G, Voss N, Gascoyne R, Zhou Y. Aberrant expression of T-plastin in Sezary cells. Cancer Res. 63: 7122-7127, 2003.
8. Campos EI, Martinka M, Mitchell DL, Dai DL, Li G. Mutations of the ING1 tumor suppressor gene detected in human melanoma abrogate nuclear excision repair. Int. J. Oncol. 25:73-80, 2004.
9. Dai DL, Martinka M, Bush JA, Li G. Reduced Apaf-1 expression in human cutaneous melanoma. Br. J. Cancer 91:1089-1095, 2004.
10. Zhou Y, Dai DL, Martinka M, Su M, Zhang Y, Campos EI, Dorocicz I, Tang L, Nelson C, Ho V, Li G. Osteopontin expression correlates with melanoma invasion and promotes cell growth. J. Invest. Dermatol. 124:1044-1052, 2005.
11. Ho CK, Li G. Mutant p53 melanoma cell lines respond differently to CP-31398-induced apoptosis. Br. J. Dermatol. 153: 900-910, 2005.
12. Tang L, Dai D, Su M, Martinka M, Li G, Zhou Y. Aberrant expression of collagen triple helix repeat containing 1 (CTHRC1): Association with melanoma progression and prevalence in human solid cancers. Clin. Cancer Res. 12:3716-3722, 2006.
13. Karst AM, Li G. BH3-only proteins in tumorigenesis and malignant melanoma. Cell. Mol. Life Sci. 64:318-330, 2007.
14. Kuo WH, Wang Y, Wong RPC, Campos EI, Li G. The ING1b protein facilitates accessibility to damaged nucleosomal DNA. Exp. Cell Res. 313:1628-1638, 2007.
15. Wang Y, Dai DL, Martinka M, Li G. Prognostic significance of ING3 subcellular localization in human cutaneous melanoma. Clin. Cancer Res. 13: 4111-4116, 2007.
16. Garate M, Campos EI, Bush JA, Xiao H, Li G. Phosphorylation of the tumor suppressor p33ING1b at Ser126 influences its protein stability and cell proliferation. FASEB J. 21:3705-3716, 2007.
17. Dai DL, Wang Y, Liu M, Martinka M, Li G. Reduced Bim expression in human cutaneous melanomas. J. Invest. Dermatol. (in press)
18. Wong RPC, Khosravi S, Martinka M, Li G. Mcl-1 expression is overexpressed in dysplastic nevi and melanoma. Oncol. Rep. (in press)

©2008