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Sci Rep. 2017 Oct 23;7(1):13734. doi: 10.1038/s41598-017-14033-4.

The Src family kinase LCK cooperates with oncogenic FLT3/ITD in cellular transformation.

Author information

1
Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Medicon Village, Lund, Sweden.
2
Lund Stem Cell Center, Department of Laboratory Medicine, Lund University, Lund, Sweden.
3
Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Medicon Village, Lund, Sweden. lars.ronnstrand@med.lu.se.
4
Lund Stem Cell Center, Department of Laboratory Medicine, Lund University, Lund, Sweden. lars.ronnstrand@med.lu.se.
5
Division of Oncology, Skåne University Hospital, Lund, Sweden. lars.ronnstrand@med.lu.se.

Abstract

The non-receptor tyrosine kinase LCK belongs to the SRC family of kinases. SRC family kinases are proto-oncogenes that have long been known to play key roles in cell proliferation, motility, morphology and survival. Here we show that LCK regulates the function of the type III receptor tyrosine kinase FLT3 in murine pro-B cells. We observed that expression of LCK significantly enhances the colony forming capacity of the constitutively active FLT3 mutant FLT3-ITD (internal tandem duplication). Furthermore, cells expressing LCK developed tumor earlier compared to cells transfected with empty control vector. Staining of the tissues from mouse xenografts showed higher Ki67 staining in cells expressing LCK suggesting that expression of LCK enhances the FLT3-ITD-mediated proliferative capacity. LCK expression did not affect either FLT3-WT or FLT3-ITD -induced AKT, ERK1/2 or p38 phosphorylation. However, LCK expression significantly enhanced FLT3-ITD-mediated STAT5 phosphorylation. Taken together, our data suggest that LCK cooperates with oncogenic FLT3-ITD in cellular transformation.

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