American Association for Cancer Research
15417786mcr160007-sup-159993_2_supp_3502965_37g043.pptx (49.69 kB)

Figure S6: Proliferation of shFAK-expressing 8505C orthotopic tumors is not significantly inhibited. from FAK Expression, Not Kinase Activity, Is a Key Mediator of Thyroid Tumorigenesis and Protumorigenic Processes

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posted on 2023-04-03, 17:07 authored by Brittelle E. Kessler, Vibha Sharma, Qiong Zhou, Xia Jing, Laura A. Pike, Anna A. Kerege, Sharon B. Sams, Rebecca E. Schweppe

Ki67 staining of 8505C shFAK and Scrambled orthotopic thyroid tumors was performed. Proliferation was measured by the percent of Ki67 positive cells scored by a pathologist. Results are % Ki67 {plus minus} SEM.







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.Implications: 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.