scholarly journals Building the muscle pattern: Role of Retinoic acid signaling in extraocular muscle morphogenesis

2017 ◽  
Vol 145 ◽  
pp. S83-S84
Author(s):  
Glenda Comai ◽  
Alexandre Robert-Moreno ◽  
Valerie Dupé ◽  
Muriel Rhinn ◽  
Norbert Ghyselinck ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Extraocular Muscle ◽  
Retinoic Acid Signaling

Role of Retinoic Acid Signaling in the Differentiation of Spermatogonia

2017 ◽  
pp. 133-146 ◽  
Author(s):  
My-Thanh Beedle ◽  
Cathryn A. Hogarth ◽  
Michael D. Griswold
Keyword(s):  
Retinoic Acid ◽  
Retinoic Acid Signaling

scholarly journals Effects of retinoic acid signaling on extraocular muscle myogenic precursor cells in vitro

2017 ◽  
Vol 361 (1) ◽  
pp. 101-111 ◽  
Author(s):  
Sadie L. Hebert ◽  
Krysta R. Fitzpatrick ◽  
Samantha A. McConnell ◽  
Anja Cucak ◽  
Ching Yuan ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Extraocular Muscle ◽  
Precursor Cells ◽  
Retinoic Acid Signaling ◽  
Myogenic Precursor

Suppressive role of OGT-mediated O-GlcNAcylation of BAP1 in retinoic acid signaling

2017 ◽  
Vol 492 (1) ◽  
pp. 89-95 ◽  
Author(s):  
Seungtae Moon ◽  
Yong-Kyu Lee ◽  
Sang-Wang Lee ◽  
Soo-Jong Um
Keyword(s):  
Retinoic Acid ◽  
Retinoic Acid Signaling

scholarly journals The role of Zic transcription factors in regulating hindbrain retinoic acid signaling

2013 ◽  
Vol 13 (1) ◽  
pp. 31 ◽  
Author(s):  
Danna L Drummond ◽  
Caroline S Cheng ◽  
Lyndsay G Selland ◽  
Jennifer C Hocking ◽  
Lisa B Prichard ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Retinoic Acid ◽  
Retinoic Acid Signaling

Inhibition of Axl Kinase Reverses the Mesenchymal Phenotype in Leukemic Cells through the Disruption of Retinoic Acid Signaling

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3253-3253
Author(s):  
Katherine K. Soh ◽  
Brigham L. Bahr ◽  
Jeremiah J. Bearss ◽  
Wontak Kim ◽  
Peter Peterson ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Retinoic Acid ◽  
Mrna Expression ◽  
Leukemic Cells ◽  
Leukemia Cells ◽  
Mrna Levels ◽  
Retinoic Acid Signaling ◽  
Mesenchymal Phenotype

Abstract Mesenchymal stem cells (MSCs) contribute to the regeneration of mesenchymal tissues, and are essential in providing support for the growth and differentiation of primitive hemopoietic cells within the bone marrow microenvironment. It is becoming increasingly clear that the tumor microenvironment plays a very important role in tumor progression and drug resistance, and the selection of cancer cells possessing the mesenchymal phenotype leads to drug resistance in many different tumor types. We have been exploring the role of the protein Axl in promoting the mesenchymal phenotype in both myeloid and lymphoid malignancies, and the role of Axl in promoting drug resistance in these malignancies. The signaling downstream of Axl that leads to the acquisition of the mesenchymal phenotype has not been well elucidated. Following results from a genetic screen using a zebrafish model, we have discovered a role for retinoic acid (RA) signaling which is regulated by Axl and controls the mesenchymal phenotype in leukemic cells. In addition, recent reports have shown an interaction between a retinoic acid regulated gene, RARRES1, and Axl, leading our group to seek to understand the role of retinoic acid signaling in the control of AXL. We hypothesized that treatment with our AXL inhibitor, TP-0903, would disrupt RA signaling and lead to a reversal of the mesenchymal phenotype in leukemia cells. Following TP-0903 treatment, we interrogated changes in mRNA expression using RT-PCR, protein expression using standard immunoblotting, and endogenous RA levels using a competitive ELISA. We also assessed the effect of TP-0903 on tumor growth in an in vivo model, assessing efficacy of TP-0903 in an MV4-11 xenograft mouse model. One of the genes that we detected being dramatically changed by treatment with TP-0903 was the RA metabolizing protein CYP26A1, suggesting that Axl inhibition indeed leads to changes in RA metabolism. We observed a strong induction of CYP26 mRNA expression following RA treatment in MV4-11 leukemia cells which was also observed in treatment with our AXL inhibitor, TP-0903, at levels as low as 100 nM. We also assessed TP-0903 activity in additional cell lines (HL60, A549, and H1650), and with an alternative AXL inhibitor, R428. Importantly, TP-0903 treatment correlated with increased CYP26 expression and reduced levels of endogenous RA. In vivo, TP-0903 strongly inhibited xenograft tumor volumes by up to 100% with multiple dose levels and treatment schedules. CYP26 expression in fixed tissues correlated well with mRNA levels observed in xenograft tumors following treatment. Taken together, our observations support our hypothesis that inhibition of AXL kinase by TP-0903 can disrupt RA metabolism by inducing CYP26 expression and this disruption of RA metabolism leads to reversal of the mesenchymal phenotype in leukemic cells. Disclosures Soh: Tolero Pharmaceuticals: Employment. Bahr:Tolero Pharmaceuticals: Employment. Bearss:Tolero Pharmaceuticals: Employment. Kim:Tolero Pharmaceuticals: Employment. Peterson:Tolero Pharmaceuticals: Employment. Whatcott:Tolero Pharmaceuticals: Employment. Siddiqui-Jain:Tolero Pharmaceuticals: Employment. Bearss:Tolero Pharmaceuticals: Employment. Warner:Tolero Pharmaceuticals: Employment.

Sign in / Sign up

Export Citation Format

Share Document