IL-7 splicing variant IL-7δ5 induces EMT and metastasis of human breast cancer cell lines MCF-7 and BT-20 through activation of PI3K/Akt pathway.
Our previous study has confirmed that IL-7δ5 (an IL-7 variant lacking exon 5) promotes breast cancer growth. However, whether IL-7δ5 is involved in tumor cell EMT and metastasis remains unclear. In this study, we investigated the preclinical effects and molecular mechanisms of IL-7δ5 on EMT and metastasis in human MCF-7 and BT-20 breast cancer cells in vitro and in vivo. The results showed that IL-7δ5 induced EMT and invasion in tumor cells, associated with up-regulation of N-cadherin and the down-regulation of E-cadherin. Furthermore, we found that IL-7δ5 induced the activation of Akt. Inhibition of PI3K/Akt pathway by LY294002 reversed the EMT transition in breast cancer cell lines MCF-7 and BT-20 induced by IL-7δ5. In addition, IL-7δ5 enhanced cancer metastasis and shortened survival time, with increased level changes of activated Akt in nude mice with breast cancer. In conclusion, our findings demonstrate that IL-7δ5 induces human breast cancer cell lines EMT and metastasis via activation of PI3K/Akt pathway. Thus, IL-7δ5 may be a potential target against human breast cancer.
Department of Pharmacology, School of Pharmacy, Guangxi Medical University, Nanning, 530021, Guangxi, People's Republic of China, yanglz2005@126.com.
Jie
J
Yang
Zhi
Z
Zeng
Yuyu
Y
Peng
Jianhua
J
Chen
Ling
L
Pan
Deshun
D
Pan
D017398:Alternative Splicing / Q000235:genetics*; D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D015820:Cadherins / Q000096:biosynthesis; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000008:administration & dosage / Q000494:pharmacology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000235:genetics*; D005260:Female; D006801:Humans; D015851:Interleukin-7 / Q000235:genetics* / Q000378:metabolism; D061986:MCF-7 Cells; D051379:Mice; D008819:Mice, Nude; D058990:Molecular Targeted Therapy; D009025:Morpholines / Q000008:administration & dosage / Q000494:pharmacology; D009362:Neoplasm Metastasis / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016019:Survival Analysis; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D015820:Cadherins; D002867:Chromones; D015851:Interleukin-7; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one