Literature DB >> 26124007

BMP-2 induces motility and invasiveness by promoting colon cancer stemness through STAT3 activation.

Bo Ram Kim1, Sang Cheul Oh2, Dae-Hee Lee2, Jung Lim Kim2, Suk Young Lee2, Myoung Hee Kang3, Sun Il Lee4, Sanghee Kang4, Sung Yup Joung4, Byung Wook Min5.   

Abstract

Bone morphogenetic proteins (BMPs) have been involved in metastatic progression and tumorigenesis of many cancer types. However, it remains unclear how BMP-2 contributes to the initiation and development of these cancers. Here, we investigated the role of BMP-2 in colon cancer stem cell (CSC) development from colon cancer cells. We also determined the effects of BMP-2 on CSC development and epithelial-mesenchymal transition (EMT) in human colon cancer cell lines HCT-116 and SW620. We found that BMP-2 enhanced sphere formation of colon cancer cells without serum. Also, BMP-2-induced spheres displayed up-regulation of stemness markers (CD133+ and EpCAM+) and increased drug resistance, hallmarks of CSCs. Importantly, expression of EMT activators p-Smad1/5 and Snail and N-cadherin was increased in the spheres' cells, indicating that BMP-2 signaling might result in CSC self-renewal and EMT. Furthermore, siRNA-mediated knockdown of signal transducer and activator of transcription 3 (STAT3) in HCT-116 cells reversed BMP-2-induced EMT and stem cell formation. Taken together, our results suggest that the BMP-2 induced STAT3-mediated induction of colon cancer cell metastasis requires an EMT and/or changes in CSC markers.

Entities:  

Keywords:  Bone morphogenetic proteins; Cancer stem cells; Colon cancer; Epithelial-mesenchymal transition; Signal transducer and activator of transcription 3

Mesh:

Substances:

Year:  2015        PMID: 26124007     DOI: 10.1007/s13277-015-3681-y

Source DB:  PubMed          Journal:  Tumour Biol        ISSN: 1010-4283


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