Abstract #2218: Leptin induces migration of breast cancer cells via upregulation of anti-apoptotic protein, survivin

Obesity is an independent risk factor for breast cancer and obese breast cancer patients exhibit a higher risk for larger tumor burden and increased metastasis. Obesity affects carcinogenesis by autocrine and paracrine effects of the adipocytokine leptin. Leptin, a product of the obese (ob) gene, has been found to play a role in tumor progression and metastasis in addition to its functions in maintaining energy balance and satiety. Previously we found that leptin induces breast cancer growth by overexpressing cyclin D1 via Stat3 activation. More recently we showed that leptin crosstalks with IGF1 signaling and increases metastatic properties of breast cancer cells by transactivating epidermal growth factor receptor (EGFR). In the present study, we investigated the molecular mechanisms underlying leptin-induced migration of breast cancer cells. We found that leptin increases expression of anti-apoptotic protein, survivin in both estrogen receptor positive and negative breast cancer cells whereas no change was observed in the expression of X-linked inhibitor of apoptosis (XIAP). Our results show that leptin treatment increases migration of breast cancer cells. Further molecular analysis showed that leptin induced migration of breast cancer cells involves upregulation of survivin as overexpression of survivin further increases leptin-induced breast cancer cell migration. Intriguingly, silencing of survivin abrogates the effect of leptin on breast cancer cell migration. Taken together, these data suggest a novel mechanism involving survivin by which leptin increases migration of breast cancer cells. Our findings indicate a novel role of anti-apoptotic protein, survivin and putforth survivin as a potential therapeutic target to inhibit breast cancer cell migration.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2218.