G9a Correlates with VLA-4 Integrin and Influences the Migration of Childhood Acute Lymphoblastic Leukemia Cells

Cancers
Elena MadrazoJavier Redondo-Muñoz

Abstract

Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer. As ALL progresses, leukemic cells cross the endothelial barrier and infiltrate other tissues. Epigenetic enzymes represent novel therapeutic targets in hematological malignancies, and might contribute to cells' capacity to migrate across physical barriers. Although many molecules drive this process, the role of the nucleus and its components remain unclear. We report here, for the first time, that the expression of G9a (a histone methyltransferase related with gene silencing) correlates with the expression of the integrin subunit α4 in children with ALL. We have demonstrated that G9a depletion or its inhibition with BIX01294 abrogated the ability of ALL cells to migrate through an endothelial monolayer. Moreover, G9a-depleted and BIX01294-treated cells presented bigger nuclei and more adherent phenotype than control cells on endothelial monolayers. Blocking G9a did not affect the cell cytoskeleton or integrin expression of ALL cell lines, and only its depletion reduced slightly F-actin polymerization. Similarly to the transendothelial migration, G9a inhibition impaired the cell migration induced by the integrin VLA-4 (α4β1) of primary cells and ALL cell lin...Continue Reading

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Jul 8, 2017·Cancers·Elena MadrazoJavier Redondo-Muñoz

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Citations

Feb 21, 2019·Nucleus·Marcel DregerJavier Redondo-Muñoz
Jun 13, 2020·Frontiers in Cell and Developmental Biology·Gabi Gerlitz
Sep 6, 2020·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Amandda Évelin Silva-CarvalhoFelipe Saldanha-Araujo
Jan 12, 2021·Frontiers in Oncology·Hye Na KimYong-Mi Kim

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Methods Mentioned

BETA
PCR
transfection
FACS
flow cytometry

Software Mentioned

BD CellQuest Pro
Imaris
GraphPad
ImageJ
Roche
Prism

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