Background: Sip1/Tuftelin Interacting Protein (STIP) is highly
conserved from Caenorhabditis elegans to Homo sapiens and has essential
biological functions. However, its function in leukemia remains unknown.
Methods: Clinic samples and cell model were used in this article to
investigate the expression of STIP in lymphoblastic leukemia. The functional
research of STIP was performed in ARH-77 by siRNA transfection,
immunofluorescence, cell count, cell cycle analysis, qRT-PCR, sub-cellular
fractionation assays, immunoprecipitation and western blotting.
Results: Here, we found that STIP is more highly expressed in both clinical
lymphoblastic leukemia samples and cultured leukemia cells than in normal
samples. Knockdown of STIP in B lymphoblastic leukemia ARH-77 cells leads to S phase
arrest, lower cell proliferation rates, and suppressed AKT and ERK1/2 signaling pathways.
Interestingly, when protein phosphatase was inhibited by Calyculin A, STIP knockdown did
not result in the dephosphorylation of p-ERK1/2, suggesting the dependence of STIP on
protein phosphatase in the regulation of ERK1/2. Among those protein phosphatase inhibited
by Calyculin A, PP1γ was found to interact with STIP proven by immunofluorescence and
immunoprecipitation assays. The binding of STIP with PP1γ may decrease the phosphatase
activity of PP1γ, resulting in hyper-activated ERK1/2 signaling.
Conclusion: In summary, the high expression and activation effect on the ERK1/2 signaling
of STIP in lymphoblastic leukemia suggest that STIP would be a potential therapy target or
diagnosis marker for leukemia.