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The FOXM1/ATX signaling contributes to pancreatic cancer development

Dacheng Xie1, Shijun Yu1, Li Li1

  • 1Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine Shanghai 200120, China.

American Journal of Translational Research
|September 11, 2020
PubMed

Insights

Autotaxin (ATX) is a target of Forkhead Box M1 (FOXM1) and promotes pancreatic cancer growth. Together, ATX and FOXM1 form a feedback loop that drives pancreatic ductal adenocarcinoma progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Autotaxin (ATX) and Forkhead Box M1 (FOXM1) are known oncogenes in various human cancers.
  • The roles of ATX and its relationship with FOXM1 in pancreatic ductal adenocarcinoma (PDAC) remain unclear.

Purpose of the Study:

  • To investigate the correlation between ATX and FOXM1 in PDAC.
  • To elucidate the biological functions and consequences of their interaction in PDAC development.

Main Methods:

  • Dual luciferase reporter assays and chromatin immunoprecipitation assays were used to determine the transcriptional relationship between ATX and FOXM1.
  • Cellular functional experiments assessed the impact of ATX on FOXM1-mediated cell proliferation and migration.
  • Molecular biological experiments examined the effect of ATX on FOXM1 expression via the Hippo signaling pathway.
  • Immunohistochemistry (IHC) was employed to evaluate ATX and FOXM1 expression in PDAC tissues.

Main Results:

  • ATX was identified as a downstream transcriptional target of FOXM1.
  • ATX is essential for FOXM1-driven proliferation and migration of PDAC cells.
  • ATX enhances FOXM1 expression by inhibiting the Hippo signaling pathway, establishing a positive feedback loop.
  • Both ATX and FOXM1 are frequently upregulated in PDAC tissues compared to normal tissues, with their expression levels positively correlated.

Conclusions:

  • A positive feedback loop exists between ATX and FOXM1 in PDAC.
  • This ATX-FOXM1 loop significantly promotes PDAC cell proliferation and migration.
  • Targeting this loop may offer a therapeutic strategy for pancreatic cancer.
Keywords:
ATXFOXM1migrationpancreatic cancerproliferation

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