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Regulation of Multicellular Spheroids by MAPK and FYN Kinase

Casey Lee1, Daniel M Ramos2

  • 1Department of Orofacial Sciences, University of California at San Francisco, San Francisco, CA, U.S.A.

Anticancer Research
|July 29, 2016
PubMed

Insights

Oral squamous cell carcinoma (SCC) progression in multicellular spheroids (MCS) mimics epithelial to mesenchymal transition. This process requires specific integrin subunits and signaling pathways like MAPK and FYN kinase for SCC growth.

Area of Science:

  • Oral oncology
  • Cancer biology
  • Cellular signaling

Background:

  • Oral squamous cell carcinoma (SCC) biology remains poorly understood, with stagnant 5-year survival rates around 50%.
  • The rise of Human Papilloma Virus-associated SCC necessitates deeper investigation into disease mechanisms.
  • The 3-dimensional multicellular spheroid (MCS) model offers a more accurate system for evaluating SCC behavior.

Purpose of the Study:

  • To investigate the biological mechanisms underlying SCC growth within a 3D multicellular spheroid (MCS) model.
  • To identify key molecular players, including integrins and signaling pathways, involved in SCC progression in MCS.

Main Methods:

  • Utilized a 3-dimensional multicellular spheroid (MCS) model to study oral squamous cell carcinoma (SCC) growth.
  • Investigated the role of the full-length β6 integrin subunit in MCS organization.
  • Examined the involvement of mitogen-activated protein kinase (MAPK) and FYN kinase in SCC maintenance and progression within MCS.

Main Results:

  • SCC growth within MCS models approximates epithelial to mesenchymal transition (EMT).
  • The organization of MCS requires the full-length β6 integrin subunit.
  • Maintenance of MCS structure and SCC progression involves mitogen-activated protein kinase (MAPK) and FYN kinase signaling, impacting key cell adhesion molecules like E-cadherin, β-catenin, and N-cadherin, as well as SNAIL expression.

Conclusions:

  • The 3D multicellular spheroid (MCS) model effectively recapitulates complex microenvironmental and growth patterns of oral squamous cell carcinoma (SCC).
  • Epithelial to mesenchymal transition (EMT) is a key feature of SCC growth in MCS.
  • Both MAPK and FYN kinase signaling pathways are critical for the maintenance and progression of SCC within the MCS microenvironment.
Keywords:
FYN KinaseMAP kinaseSpheroidmulticellular spheroid formation

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