NMIIA promotes tumor growth and metastasis by activating the Wnt/β-catenin signaling pathway and EMT in pancreatic cancer

Abstract

Non-muscle myosin IIA (NMIIA) protein plays an important role in cell cytokinesis and cell migration. The role and underlying regulatory mechanisms of NMIIA in pancreatic cancer (PC) remain elusive. We found that NMIIA is highly expressed in PC tissues and contributes to PC poor progression by using open microarray datasets from the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and PC tissue arrays. NMIIA regulates β-catenin mediated EMT to promote the proliferation, migration, invasion, and sphere formation of PC cells in vitro and in vivo. NMIIA controls the β-catenin transcriptional activity by interacting with β-catenin. Moreover, MEK/ERK signaling is critical in MLC2 (Ser19) phosphorylation, which can mediate NMIIA activity and regulate Wnt/β-catenin signaling. These findings highlight the significance of NMIIA in tumor regression and implicate NMIIA as a promising candidate for PC treatment.

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Data availability

All data generated or analysed during this study are included in this published article and its supplementary information files.

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Funding

This work was supported by National Natural Science Foundation of China (grant 81370600, DL); The Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning (TP2015022, DL); Shanghai Pujiang Program (15PJ1404800, DL); Innovation Program of Shanghai Municipal Education Commission (15ZZ056, DL); and Innovation Program for Ph.D. students in Shanghai Jiaotong University School of Medicine (BXJ201731).

Authors’ contributions

Study design and concept: LD, ZPT. Data acquisition: ZPT, LYY, LB, LYH. Data analysis and interpretation: ZPT. Manuscript preparation: ZPT, LB, LD. Manuscript review: LD, YY, LB. All authors read and approved the final manuscript.

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Correspondence to Yuanhua Liu or Yuan Yao or Dong Li.

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All procedures of human and mouse experiments were approved by Ethics Committee of Shanghai Ninth People’s Hospital affiliated to Shanghai JiaoTong University, School of Medicine.

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Zhou, P., Li, Y., Li, B. et al. NMIIA promotes tumor growth and metastasis by activating the Wnt/β-catenin signaling pathway and EMT in pancreatic cancer. Oncogene 38, 5500–5515 (2019). https://doi.org/10.1038/s41388-019-0806-6

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