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Neutrophil Extracellular Traps Generated by Low Density Neutrophils Obtained from Peritoneal Lavage Fluid Mediate Tumor Cell Growth and Attachment
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SKAP1 Expression in Cancer Cells Enhances Colon Tumor Growth and Impairs Cytotoxic Immunity by Promoting Neutrophil

Jian Gao1, Jun Liu2, Jilin Lu2

  • 1State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200032, China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|September 13, 2024
PubMed

Insights

Src kinase associated phosphoprotein 1 (SKAP1) promotes colon cancer growth by enhancing neutrophil extracellular traps (NETs). Targeting SKAP1 or its downstream pathway may offer new therapeutic strategies for colon cancer.

Area of Science:

  • Oncology
  • Immunology

Background:

  • Colon cancer mechanisms remain incompletely understood.
  • Src kinase associated phosphoprotein 1 (SKAP1) is identified as a novel gene linked to colon cancer.
  • Elevated SKAP1 expression correlates with poor patient survival.

Purpose of the Study:

  • To investigate the role of SKAP1 in colon cancer development and progression.
  • To elucidate the mechanisms underlying SKAP1-mediated tumor promotion.
  • To explore SKAP1 as a potential therapeutic target.

Main Methods:

  • Analysis of SKAP1 expression in colon cancer cells and patient data.
  • In vivo and in vitro studies to assess SKAP1's tumor-promoting effects.
  • Investigation of immune cell infiltration, neutrophil extracellular trap (NET) formation, and related signaling pathways (NFATc1, CXCL8).
  • Evaluation of therapeutic interventions targeting SKAP1, NETs, and adoptive natural killer cell therapy.

Main Results:

  • SKAP1 expression is significantly upregulated in colon cancer and predicts poor survival.
  • SKAP1 promotes colon tumor growth in vivo, involving neutrophils and enhanced NET formation.
  • SKAP1 upregulates CXCL8 via NFATc1, driving neutrophil infiltration and NETs.
  • Blocking CXCL8 or NFATc1 mitigates SKAP1-induced tumor promotion.
  • Inhibition of SKAP1-induced NETs enhances adoptive natural killer cell therapy efficacy.

Conclusions:

  • SKAP1 promotes colon cancer growth through a novel axis involving cancer cell/neutrophil NFATc1/CXCL8/NETs.
  • SKAP1 represents a potential therapeutic target for colon cancer treatment.
  • Targeting the SKAP1-NET axis could improve immunotherapy outcomes.
Keywords:
CXCL8NFATc1SKAP1colon cancerneutrophil extracellular trap

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