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Author Notes:

Correspondence to: William Tse, email: william.tse@louisville.edu.

We thank Helen Kim for her editorial assistance and Dr. Donghoon Chung for experimental design and technical advice. This work was supported by the use of the facilities of the James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky.

Conflict of Interest: The authors declare no conflict of interest.

Subjects:

Research Funding:

This work was partly supported by the NIH R01DK059380 (KB).

RM was supported by grants SFB-F2807 and SFB-F4707 from the Austrian Science Fund (FWF).

JJ was supported by grants from the University of Louisville School of Medicine and the Elsa U. Pardee Foundation.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Oncology
  • Cell Biology
  • AF1q
  • STAT3
  • PDGF
  • PDGFR
  • Src
  • BREAST-CANCER
  • GROWTH-FACTOR
  • MOLECULAR TARGETS
  • FUNCTIONAL-ROLE
  • TUMOR-GROWTH
  • CELLS
  • ACTIVATION
  • EXPRESSION
  • PATHWAYS

MLLT11/AF1q boosts oncogenic STAT3 activity through Src-PDGFR tyrosine kinase signaling

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Journal Title:

Oncotarget

Volume:

Volume 7, Number 28

Publisher:

, Pages 43960-43973

Type of Work:

Article | Final Publisher PDF

Abstract:

Constitutive STAT3 activation by tyrosine phosphorylation of mutated or amplified tyrosine kinases (pYSTAT3) is critical for cancer initiation, progression, invasion, and motility of carcinoma cells. We showed that AF1q is associated with STAT3 signaling in breast cancer cells. In xenograft models, enhanced AF1q expression activated STAT3 and promoted tumor growth and metastasis in immunodeficient NSG mice. The cytokine secretory phenotype of MDA-MB-231LN breast cancer cells with altered AF1q expression revealed changes in expression of platelet-derived growth factor subunit B (PDGF-B). AF1q-induced PDGF-B stimulated motility, migration, and invasion of MDA-MB-231LN cells, and AF1q up-regulated platelet-derived growth factor receptor (PDGFR) signaling. Further, AF1q-induced PDGFR signaling enhanced STAT3 activity through Src kinase activation, which could be blocked by the Src kinase inhibitor PP1. Moreover, AF1q upregulated tyrosine kinase signaling through PDGFR signaling, which was blockable by imatinib. In conclusion, we demonstrated that enhanced AF1q expression contributes to persistent and oncogenic pYSTAT3 levels in invasive carcinoma cells by activating Src kinase through activation of the PDGF-B/PDGFR cascade. Therefore, AF1q plays an essential role as a cofactor in PDGF-B-driven STAT3 signaling.

Copyright information:

© 2016 Park et al.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 3.0 Unported License (http://creativecommons.org/licenses/by/3.0/).

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