Skip to Content
Merck
  • FAK Expression, Not Kinase Activity, Is a Key Mediator of Thyroid Tumorigenesis and Protumorigenic Processes.

FAK Expression, Not Kinase Activity, Is a Key Mediator of Thyroid Tumorigenesis and Protumorigenic Processes.

Molecular cancer research : MCR (2016-06-05)
Brittelle E Kessler, Vibha Sharma, Qiong Zhou, Xia Jing, Laura A Pike, Anna A Kerege, Sharon B Sams, Rebecca E Schweppe
ABSTRACT

There are limited therapy options for advanced thyroid cancer, including papillary and anaplastic thyroid cancer (PTC and ATC). Focal adhesion kinase (FAK) regulates cell signaling by functioning as a scaffold and kinase. Previously, we demonstrated that FAK is overexpressed and activated in thyroid cancer cells and human PTC clinical specimens. However, it remains unclear whether patients with advanced thyroid cancer will benefit from FAK inhibition. Therefore, the dual functions of FAK in mediating protumorigenic processes and thyroid tumorigenesis were investigated. Evidence here shows that FAK expression predominantly regulates thyroid cancer cell growth, viability, and anchorage-independent growth. FAK inhibition, with PF-562,271 treatment, modestly reduced tumor volumes, while FAK depletion, through shRNA knockdown, significantly reduced tumor volumes in vivo A role for FAK expression in tumor establishment was demonstrated in a model of PTC, where FAK knockdown tumors did not develop. FAK depletion also led to a significant decrease in overall metastatic burden. Interestingly, pretreatment with a FAK inhibitor resulted in a paradoxical increase in metastasis in a model of ATC, but decreased metastasis in a model of PTC. These data provide the first evidence that FAK expression is critical for the regulation of thyroid tumorigenic functions. This study demonstrates that FAK expression, but not kinase activity alone, predominantly mediates thyroid tumor growth and metastasis, indicating that targeting the scaffolding function(s) of FAK may be an important therapeutic strategy for advanced thyroid cancer, as well as other FAK-dependent tumors. Mol Cancer Res; 14(9); 869-82. ©2016 AACR.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
PF-562,271, ≥98% (HPLC)
SKU
Pack Size
Availability
Price
Quantity