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PLA2R1 Inhibits Differentiated Thyroid Cancer Proliferation and Migration via the FN1-Mediated ITGB1/FAK Axis

Hui Zheng1, Mengyu Zhang1, Dingwei Gao1

  • 1Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200092, China.

Cancers
|June 22, 2023
PubMed

Insights

Phospholipase A2 Receptor 1 (PLA2R1) is underexpressed in thyroid cancer, inhibiting cell proliferation and migration. PLA2R1 may serve as a therapeutic target for differentiated thyroid cancer (DTC).

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Phospholipase A2 Receptor 1 (PLA2R1) is implicated in various cancers.
  • Its specific role in thyroid cancer remains unclear.
  • Understanding PLA2R1's mechanism is crucial for thyroid cancer research.

Purpose of the Study:

  • To investigate the role and mechanism of PLA2R1 in differentiated thyroid cancer (DTC).
  • To evaluate PLA2R1 as a potential diagnostic marker and therapeutic target for DTC.

Main Methods:

  • Immunohistochemical staining of 115 clinical thyroid cancer specimens.
  • In vitro studies using thyroid cancer cell lines (8505c, FTC133) with PLA2R1 manipulation.
  • CCK8 and wound healing assays to assess cell proliferation and migration.
  • Co-immunoprecipitation (Co-IP) and Western blotting to elucidate molecular mechanisms.
  • In vivo studies to evaluate DTC growth.

Main Results:

  • PLA2R1 expression was significantly lower in DTC tumor tissues compared to para-cancerous tissues.
  • Overexpression of PLA2R1 suppressed thyroid cancer cell proliferation and migration.
  • Knockdown of PLA2R1 partially reversed these suppressive effects.
  • PLA2R1 knockdown alleviated in vivo DTC growth.
  • Mechanistically, PLA2R1 inhibits the FAK/EMT axis by competing with FN1 for ITGB1 binding.

Conclusions:

  • PLA2R1 plays an inhibitory role in thyroid cancer progression.
  • PLA2R1 functions by modulating the FAK/EMT signaling pathway.
  • PLA2R1 represents a potential diagnostic biomarker and therapeutic target for differentiated thyroid cancer.
Keywords:
FN1ITGB1/FAKPLA2R1migrationthyroid cancer

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