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The interferon-β/STAT1 axis drives the collective invasion of skin squamous cell carcinoma with sealed intercellular

Yuji Kumagai1, Junko Nio-Kobayashi2, Seiichiro Ishihara3

  • 1Division of Life Science, Graduate School of Life Science, Hokkaido University, N10-W8, Kita-ku, Sapporo, 060-0810, Japan.

Oncogenesis
|May 23, 2022
PubMed

Insights

Cancer cells invade collectively through sealed spaces, driven by Interferon-beta and STAT1 activation. Understanding this process, crucial for skin squamous cell carcinoma (SCC) metastasis, could lead to better cancer treatments.

Area of Science:

  • Oncology
  • Cell Biology
  • Dermatology

Background:

  • Collective invasion, where cancer cells invade as a cluster, is linked to metastasis and poor patient prognosis.
  • Inhibiting collective invasion is a potential strategy for improving cancer treatment outcomes.
  • The specific cellular characteristics driving collective invasion are not well understood.

Purpose of the Study:

  • To investigate the cellular mechanisms underlying collective invasion in human skin squamous carcinoma cells.
  • To identify key molecular players and intercellular structures involved in collective invasion.
  • To explore the role of STAT1 and Interferon-beta in regulating collective invasion.

Main Methods:

  • Establishment of subclones with varying invasive potentials from human skin squamous carcinoma cells.
  • Microscopic analysis of intercellular spaces and cellular structures in invasive cell clusters.
  • Immunolocalization of Interferon-beta and assessment of STAT1 activation.
  • Co-culture experiments with high- and low-invasive subclones.
  • Tissue microarray analysis of human skin squamous cell carcinoma (SCC) samples.

Main Results:

  • Highly invasive subclones exhibited sealed, narrow intercellular spaces, while low-invasive subclones had open, wide spaces.
  • Interferon-beta localized to sealed intercellular spaces, activating STAT1 and promoting collective invasion.
  • Low-invasive subclones with deficient STAT1 activity lacked Interferon-beta localization and collective invasion.
  • In mixed cultures, highly invasive cells at the front promoted collective invasion by low-invasive cells.
  • Human SCC tissues showed STAT1 enrichment at the invasive front.

Conclusions:

  • Intercellular structure plays a critical role in regulating collective invasion potential.
  • STAT1 activation, modulated by Interferon-beta within sealed intercellular spaces, is a key driver of collective invasion in SCC.
  • Targeting intercellular structures and STAT1 signaling may offer novel therapeutic strategies for SCC.

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