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ATPR regulates human mantle cell lymphoma cells differentiation via SOX11/CyclinD1/Rb/E2F1

Xiaoling Xu1, Tao Zhang1, Meiju Zhang1

  • 1The Key Laboratory of Inflammation and Immune Medicated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, Anhui, China; The Key Laboratory of Anti-inflammatory and Immune Medicines, Ministry of Education, Hefei, Anhui, China.

Cellular Signalling
|February 13, 2022
PubMed

Insights

4-amino-2-trifluoromethyl-phenyl retinate (ATPR) effectively treats mantle cell lymphoma (MCL) by inducing cell differentiation and downregulating SOX11. This novel approach offers a promising new therapeutic avenue for MCL patients.

Area of Science:

  • Oncology
  • Hematology
  • Molecular Biology

Background:

  • Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoproliferative disorder with limited treatment options.
  • Novel therapeutic strategies targeting specific molecular pathways are urgently needed for MCL.
  • 4-amino-2-trifluoromethyl-phenyl retinate (ATPR) has shown promise in other leukemias by inducing differentiation.

Purpose of the Study:

  • To investigate the potential of ATPR as a differentiation therapy for mantle cell lymphoma (MCL).
  • To elucidate the molecular mechanisms underlying ATPR's effects on MCL cells, focusing on SOX11 and the CyclinD1/Rb/E2F1 axis.

Main Methods:

  • Treatment of JEKO-1 and MINO MCL cell lines with ATPR.
  • Assessment of cell proliferation and differentiation.
  • Analysis of SOX11 expression levels (downregulation via ATPR, silencing, and overexpression).
  • Investigation of the CyclinD1/Rb/E2F1 signaling pathway.

Main Results:

  • ATPR treatment completely repressed proliferation and induced differentiation in JEKO-1 MCL cells.
  • ATPR significantly downregulated the expression of the neural transcription factor SOX11 in MCL cells.
  • SOX11 manipulation (silencing or overexpression) directly impacted MCL cell proliferation and differentiation.
  • ATPR was found to regulate the CyclinD1/Rb/E2F1 axis in MCL cells.

Conclusions:

  • ATPR effectively promotes differentiation of MCL cells, offering a potential new therapeutic strategy.
  • The mechanism involves the downregulation of SOX11 and regulation of the CyclinD1/Rb/E2F1 axis.
  • This study provides a strong experimental basis for developing ATPR-based differentiation therapy for mantle cell lymphoma.
Keywords:
4-amino-2-trifluoromethyl-phenyl retinateCyclinD1/Rb/E2F1DifferentiationMantle cell lymphomaSOX11

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