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The Rho guanosine nucleotide exchange factors Vav2 and Vav3 modulate epidermal stem cell function

L Francisco Lorenzo-Martín1,2,3, Mauricio Menacho-Márquez1,2,3, Natalia Fernández-Parejo1,2

  • 1Molecular Mechanisms of Cancer Program, Centro de Investigación del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC)-University of Salamanca, 37007, Salamanca, Spain.

Oncogene
|May 9, 2022
PubMed

Insights

Vav2 and Vav3 regulate skin stem cell function and identity in both normal and cancerous conditions. These guanine nucleotide exchange factors are key to maintaining stem cell quiescence or promoting tumor growth.

Area of Science:

  • Dermatology
  • Cell Biology
  • Molecular Biology

Background:

  • Rho GTPases are crucial for skin stem cell (SSC) biology.
  • The role of upstream regulators, like Vav guanine nucleotide exchange factors (GEFs), in SSCs is not well understood.
  • Understanding these regulators is important for both normal skin homeostasis and tumorigenesis.

Purpose of the Study:

  • To investigate the function of Vav subfamily guanine nucleotide exchange factors in regulating normal and cancerous skin stem cells.
  • To elucidate the molecular mechanisms by which Vav2 and Vav3 influence SSC behavior.

Main Methods:

  • Utilized mouse models with manipulated Vav subfamily guanine nucleotide exchange factor activity (gain- and loss-of-function).
  • Analyzed the effects on hair follicle bulge stem cell number, function, and responsiveness.
  • Examined gene expression programs associated with stem cell identity, quiescence, and activation.

Main Results:

  • Vav2 and Vav3 were found to regulate the number, functional status, and responsiveness of hair follicle bulge stem cells.
  • In normal SSCs, Vav2 and Vav3 reinforce identity and promote quiescence through specific gene expression programs.
  • In cancer stem cells, Vav2 and Vav3 promote transcriptomal programs linked to identity, activation, and cytoskeletal remodeling.

Conclusions:

  • Vav2 and Vav3 play a significant role in regulating both normal and tumor epidermal stem cells.
  • These Rho exchange factors are critical for maintaining the balance between stem cell quiescence and activation in different physiological states.

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