Role of the Wnt/PI3-K Pathway in the Regulation of Beta-catenin in Melanoma Progression

• Author / Creator

  Sidhu, Jaskiran K

• Melanoma has the most rapidly rising incidence of all cancers and once metastasized it is very difficult to treat. This makes the identification of molecular pathways that are deregulated in melanoma a novel area of study. β-catenin (β-cat) is a multifunctional protein of the Wnt signaling pathway that is key in driving metastasis. Understanding what regulates the high levels of active-β-cat expressed in metastatic melanomas was the goal of this study. We looked into the PI3K pathway as the possible mediator, as PTEN the negative regulator of the pathway, is lost in 30-60% of melanomas.
  We found that there is an inverse relationship in β-cat and PTEN expression through melanoma progression. The inhibition of the PI3K pathway decreased expression of the active form of β-cat and downstream effector genes, independent of Wnt signaling. Therefore, the suppression of active-β-cat is a potential molecular target that may serve to limit metastatic progression.

• Subjects / Keywords

  • PI3-K pathway
  • Beta-catenin
  • Wnt pathway
  • Active-Beta-catenin
  • Melanoma
  • Signal transduction
  • EMT

• Graduation date

  Fall 2012

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/R3D65J

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.