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Serine peptidase inhibitor Kunitz type 2 (SPINT2) in cancer development and progression

Fernanda Marconi Roversi1, Sara Teresinha Olalla Saad1, João Agostinho Machado-Neto1

  • 1Hematology and Transfusion Medicine Center, University of Campinas/Hemocentro-UNICAMP, Campinas, São Paulo, Brazil.

Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie
|March 3, 2018
PubMed

Insights

The SPINT2 gene is often silenced in human cancers, disrupting Hepatocyte growth factor (HGF) signaling. Reactivating SPINT2 can reduce cancer cell viability, migration, and invasion, offering potential therapeutic targets.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Hepatocyte growth factor (HGF)/c-MET signaling is crucial for cancer cell proliferation, survival, migration, and motility.
  • Serine peptidase inhibitor Kunitz type 2 (SPINT2) acts as an HGF activator inhibitor (HAI), preventing the formation of bioactive HGF.

Purpose of the Study:

  • To review evidence on SPINT2's role in cancer development and progression.
  • To explore the clinical, biological, and functional aspects of SPINT2 in various neoplasias.

Main Methods:

  • Literature review of studies on SPINT2 in human cancers.
  • Analysis of gene promoter methylation and its effect on SPINT2 expression.
  • Functional assays to assess the impact of SPINT2 reactivation on cancer cell phenotypes.

Main Results:

  • The SPINT2 gene promoter is frequently methylated in a wide range of human cancers, leading to its epigenetic silencing.
  • SPINT2 reactivation in cancer cell lines significantly reduces cell viability, migration, and invasion.
  • Downregulation or silencing of SPINT2 disrupts the HGF activation/inhibition balance, promoting cancer progression.

Conclusions:

  • Epigenetic silencing or downregulation of SPINT2 is a common event in human cancers.
  • SPINT2 plays a critical role in regulating HGF signaling and its dysregulation contributes to neoplastic transformation and progression.
  • SPINT2 represents a potential therapeutic target for novel cancer treatment strategies.
Keywords:
CancerHAI-2HGFAHepatocyte growth factorSPINT2Serine peptidase inhibitor Kunitz type 2

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