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Vacuolin-1 enhances RA-induced differentiation of human myeloblastic leukemia cells: evidence for involvement of a CD11b/FAK/LYN/SLP-76 axis subject to endosomal regulation that drives late differentiation steps.

Publication ,  Journal Article
Zhu, K; Kazim, N; Yue, J; Yen, A
Published in: Cell & bioscience
November 2022

Retinoic acid(RA), an embryonic morphogen, regulates cell differentiation. Endocytosis regulates receptor signaling that governs such RA-directed cellular processes. Vacuolin-1 is a small molecule that disrupts endocytosis, motivating interest in its effect on RA-induced differentiation/arrest. In HL-60 myeloblastic-leukemia cells, RA causes differentiation evidenced by a progression of cell-surface and functional markers, CD38, CD11b, and finally reactive oxygen species(ROS) production and G1/0 cell cycle arrest in mature cells.We found that Vacuolin-1 enhanced RA-induced CD11b, ROS and G1/0 arrest, albeit not CD38. Enhanced CD11b expression was associated with enhanced activation of Focal Adhesion Kinase(FAK). Adding vacuolin-1 enhanced RA-induced tyrosine phosphorylation of FAK, Src Family Kinases(SFKs), and the adaptor protein, SLP-76, expression of which is known to drive RA-induced differentiation. Depleting CD11b cripples late stages of progressive myeloid differentiation, namely G1/0 arrest and inducible ROS production, but not expression of CD38. Loss of NUMB, a protein that supports early endosome maturation, affected RA-induced ROS and G1/0 arrest, but not CD38 expression.Hence there appears to be a novel CD11b/FAK/LYN/SLP-76 axis subject to endosome regulation which contributes to later stages of RA-induced differentiation. The effects of vacuolin-1 thus suggest a model where RA-induced differentiation consists of progressive stages driven by expression of sequentially-induced receptors.

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Published In

Cell & bioscience

DOI

EISSN

2045-3701

ISSN

2045-3701

Publication Date

November 2022

Volume

12

Issue

1

Start / End Page

179
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Zhu, Kaiyuan, Noor Kazim, Jianbo Yue, and Andrew Yen. “Vacuolin-1 enhances RA-induced differentiation of human myeloblastic leukemia cells: evidence for involvement of a CD11b/FAK/LYN/SLP-76 axis subject to endosomal regulation that drives late differentiation steps.Cell & Bioscience 12, no. 1 (November 2022): 179. https://doi.org/10.1186/s13578-022-00911-6.
Journal cover image

Published In

Cell & bioscience

DOI

EISSN

2045-3701

ISSN

2045-3701

Publication Date

November 2022

Volume

12

Issue

1

Start / End Page

179