Activation of IL-8 via PI3K/Akt-dependent pathway is involved in leptin-mediated epithelial-mesenchymal transition in human breast cancer cells

• Published in: Cancer biology & therapy 2015, Vol.16 (8), p.1220-1230
• Main Authors: Wang, Lin, Tang, Cuiping, Cao, Hong, Li, Kuangfa, Pang, Xueli, Zhong, Liang, Dang, Weiqi, Tang, Hao, Huang, Yunxiu, Wei, Lan, Su, Min, Chen, Tingmei
• Format: Article
• Language: English
• Subjects: Animals; breast cancer; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cell Line, Tumor - drug effects; Cell Movement; EMT; Epithelial-Mesenchymal Transition; Female; Humans; IL-8; Interleukin-8 - genetics; Interleukin-8 - metabolism; leptin; Leptin - metabolism; Leptin - pharmacology; MCF-7 Cells; Mice, Nude; Phosphatidylinositol 3-Kinases - metabolism; PI3K/Akt; Proto-Oncogene Proteins c-akt - metabolism; Receptors, Leptin - metabolism; Research Paper; Signal Transduction; STAT3 Transcription Factor - metabolism
• ISSN: 1538-4047; 1555-8576
• DOI: 10.1080/15384047.2015.1056409

Background Information: Previous studies have revealed that leptin may be involved in epithelial-mesenchymal transition (EMT), a crucial initiator of cancer progression to facilitate metastatic cascade, increase tumor recurrence, and ultimately cause poor prognosis. However, the underlying mechanism remains unclear. The aim of our present study was to investigate the effect of leptin on EMT of breast cancer cells and the underlying mechanism. Results: Our data demonstrated that leptin significantly increased the phosphorylation of STAT3, Akt, and ERK1/2, elevated the expression of IL-8, and induced breast cancer cells to undergo EMT. The effect of leptin on IL-8 could visibly abolished by the inhibitor of PI3K LY294002. In addition, leptin-induced EMT of breast cancer cells was blocked by anti-IL-8 antibodies. Examination of the expression of ObR, leptin, IL-8 and EMT-related biomarkers in patient specimens demonstrated that malignant breast carcinoma with lymph node metastases (LNM), which represents poor prognosis, expressed higher levels of ObR, leptin, IL-8 than other types of breast cancer, and displayed more obvious EMT transversion. In vivo xenograft experiment revealed that leptin signally promoted tumor growth and metastasis and increased the expressions of IL-8 and EMT-related biomarkers. Conclusions: Our results support that leptin-induced EMT in breast cancer cells requires IL-8 activation via the PI3K/Akt signal pathway.