Related Experiment Video

Updated: May 5, 2026

Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes
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Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes

Published on: September 28, 2018

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Shp1 phosphatase regulates CXCR2 protein stability and IL8-mediated invasiveness in breast cancer

Marcello Monti1, Pier Giorgio Amendola2, Angela Filograna1

  • 1Institute of Endotypes in Oncology, Metabolism and Immunology "G. Salvatore", National Research Council, Naples, Italy.

Cell Death & Disease
|March 2, 2026
PubMed

Insights

Inhibiting Shp1 phosphatase in breast cancer accelerates cell migration and invasiveness. Interleukin-8 (IL8) reduces Shp1 activity, impacting receptor turnover and promoting metastasis, especially in triple-negative breast cancer (TNBC).

Area of Science:

  • Oncology
  • Cell Biology
  • Biochemistry

Background:

  • Shp1 phosphatase typically inhibits tumor growth by suppressing tyrosine kinase signaling.
  • Interleukin-8 (IL8) is a chemokine implicated in promoting tumor progression within the tumor microenvironment.
  • IL8 exerts its pro-tumorigenic effects via the CXCR2 receptor, influencing intracellular signaling pathways.

Purpose of the Study:

  • To investigate the role of Shp1 in breast cancer cell migration and invasiveness.
  • To elucidate the mechanism by which IL8 modulates Shp1 activity.
  • To identify Shp1 as a potential therapeutic target in aggressive breast cancer subtypes.

Main Methods:

  • Genetic and pharmacological inhibition of Shp1 in breast cancer cell lines (MCF7).
  • Analysis of IL8-induced signaling pathways, including PKC-mediated phosphorylation of Shp1 and CXCR2.
  • Assessment of receptor ubiquitination, degradation, and cell invasiveness.
  • Transcriptomic and pathway analyses.

Main Results:

  • Shp1 inhibition enhances breast cancer cell migration and invasiveness.
  • IL8 directly reduces Shp1 enzymatic activity through PKC-mediated phosphorylation at Ser591.
  • This interaction leads to enhanced CXCR2 phosphorylation, ubiquitination, and degradation, creating a feedback loop for signal attenuation.
  • Shp1's regulation of CXCR2 impacts IL8-driven invasiveness in a subtype-specific manner, notably affecting luminal and TNBC cells.
  • Shp1 downregulation correlates with reduced survival and elevated IL8 levels in TNBC.

Conclusions:

  • Shp1 plays a critical role in regulating IL8 signaling and breast cancer cell invasiveness.
  • A novel feedback mechanism involving Shp1, IL8, and CXCR2 turnover has been identified.
  • Targeting the CXCR2-Shp1 axis presents a promising therapeutic strategy for limiting invasiveness and metastasis in aggressive breast cancers, particularly TNBC.

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