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Inhibiting HSD17B8 suppresses the cell proliferation caused by PTEN failure

Wei Zhao1,2, Ruiting Huang1, Dongyang Ran1

  • 1School of Basic Medical Sciences, Henan University, Kaifeng, Henan Province, China.

Scientific Reports
|May 29, 2024
PubMed

Insights

The tumor suppressor PTEN (phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase) interacts with HSD17B8, regulating cell division independently of PTEN

Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • The tumor suppressor PTEN homolog daf-18 in C. elegans regulates cell division during L1 arrest.
  • Established pathways involving PTEN's phosphatase activity are well-studied.
  • A novel mechanism for PTEN-mediated cell cycle control is investigated.

Purpose of the Study:

  • To identify novel regulators of cell proliferation controlled by daf-18.
  • To elucidate the mechanism by which PTEN modulates cell division independently of its phosphatase activity.
  • To explore a new protein-protein interaction involving PTEN in tumor suppression.

Main Methods:

  • Forward genetic screening in Caenorhabditis elegans (C. elegans).
  • Identification and characterization of the F12E12.11 gene and its protein product.
  • Analysis of protein-protein interactions between daf-18 and F12E12.11.
  • Investigation of the enzymatic activity of F12E12.11 (HSD17B8) and its effect on steroid hormone levels.
  • Cell cycle analysis and pathway investigation (MAPK/ERK).

Main Results:

  • A novel gene, F12E12.11, was identified as being regulated by daf-18 and impacting cell proliferation.
  • F12E12.11 is the C. elegans ortholog of human estradiol 17-beta-dehydrogenase 8 (HSD17B8).
  • PTEN physically interacts with HSD17B8, modulating its activity.
  • This interaction leads to reduced estrone and increased estradiol levels.
  • Estradiol accumulation may arrest tumor cells in G2/M phase via MAPK/ERK signaling.

Conclusions:

  • PTEN restrains cell division through an unconventional interaction with HSD17B8, independent of its phosphatase activity.
  • This interaction provides a novel mechanism for PTEN-mediated tumor suppression.
  • The findings reveal intricate molecular interactions governing cell cycle control and tumor suppression.
Keywords:
C. elegansDaf-18F12E12.11Cell proliferationMCF-7PTEN

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