GD3s, a novel drug target of cancer

[Speaker] Jinhua Wang:1,2
[Co-author] Wan Li:1,2, Jinyi Liu:1,2, Weiqi Fu:1,2, Tengfei Ji:1,2, Guanhua Du:1,2
1:The State Key Laboratory of Bioactive Substance and Function of Natural Medicines, China, 2:Key Laboratory of Drug Target Research and Drug Screen, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, China

Background: There are three major subtype breast cancers, such as ER+, HER2+, Triple Negative Breast Cancer (ER-, PR-, HER2-). Triple negative breast cancer is the most aggressive breast cancer and has a very poor prognosis. Up to now, there is no target drug for triple negative breast cancer (TNBC). It is important to identify novel drug target of TNBC and look for specific target drug of TNBC.

Methods: In silicon assay was used to analyze synthase of Ganglioside D3 (GD3s) expression in different cancers and assay association between survival rate and GD3s expression. CCK8 was used to assess the proliferation of cells. Soft agar was used to check colony formation of cells. BD Transwell chambers were used to evaluate migration and invasion of cells. Methylation specific PCR (MS-PCR) was used to check methylation level of GD3s in tissues of cancers. qRT-PCR and Western blotting were uses to check mRNA and protein expression of GD3s, SOX10, MIA, TRIM2, ROPN1 and ROPN1B in TNBC cells. GD3s expression in tissues of cancers was checked by immunohistochemistry.

Results: There was higher GD3s expression in ER negative breast cancer than that in ER positive breast cancer. GD3s was also highly expressed in TNBC compared as the other type breast cancers. GD3s was overexpressed in TNBC cells and tissues of TNBC, which was owed by hypomethylation of GD3s gene. Overexpression of GD3s promoted proliferation, migration, invasion and colony formation while inhibition of GD3s reduced proliferation, migration, invasion and colony formation. Overexpression of GD3s induced expression of SOX10 and its downstream targets MIA, TRIM2, ROPN1 and ROPN1B while knockdown of GD3s reduced expression of SOX10 and its downstream targets MIA, TRIM2, ROPN1 and ROPN1B. GD3s expression was closely associated with overall survival (OS), distant metastasis free survival (DMFS), and relapse free survival (RFS).

Conclusion: GD3s is a novel drug target of triple negative breast cancer

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