Focal adhesion kinase a potential therapeutic target for pancreatic cancer and malignant pleural mesothelioma

Rajani Kanteti, Tamara Mirzapoiazova, Jacob J. Riehm, Immanuel Dhanasingh, Bolot Mambetsariev, Jiale Wang, Prakash Kulkarni, Garima Kaushik, Parthasarathy Seshacharyulu, Moorthy P. Ponnusamy, Hedy L. Kindler, Mohd W. Nasser, Surinder K. Batra, Ravi Salgia

Research output: Contribution to journalArticlepeer-review

75 Scopus citations


The non-receptor cytoplasmic tyrosine kinase, Focal Adhesion Kinase (FAK) is known to play a key role in a variety of normal and cancer cellular functions such as survival, proliferation, migration and invasion. It is highly active and overexpressed in various cancers including Pancreatic Ductal Adenocarcinoma (PDAC) and Malignant Pleural Mesothelioma (MPM). Here, initially, we demonstrate that FAK is overexpressed in both PDAC and MPM cell lines. Then we analyze effects of two small molecule inhibitors PF-573228, and PF-431396, which are dual specificity inhibitors of FAK and proline rich tyrosine kinase 2 (PYK2), as well as VS-6063, another small molecule inhibitor that specifically inhibits FAK but not PYK2 for cell growth, motility and invasion of PDAC and MPM cell lines. Treatment with PF-573228, PF-431396 and VS-6063 cells resulted in a dose-dependent inhibition of growth and anchorage-independent colony formation in both cancer cell lines. Furthermore, these compounds suppressed the phosphorylation of FAK at its active site, Y397, and functionally induced significant apoptosis and cell cycle arrest in both cell lines. Using the ECIS (Electric cell-substrate impedance sensing) system, we found that treatment of both PF compounds suppressed adherence and migration of PDAC cells on fibronectin. Interestingly, 3D-tumor organoids derived from autochthonous KC (Kras;PdxCre) mice treated with PF-573228 revealed a significant decrease in tumor organoid size and increase in organoid cell death. Taken together, our results show that FAK is an important target for mesothelioma and pancreatic cancer therapy that merit further translational studies.

Original languageEnglish (US)
Pages (from-to)316-327
Number of pages12
JournalCancer Biology and Therapy
Issue number4
StatePublished - Apr 3 2018


  • FAK
  • PF-431396
  • PF-573228
  • VS-6063
  • mesothelioma
  • pancreatic cancer

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research


Dive into the research topics of 'Focal adhesion kinase a potential therapeutic target for pancreatic cancer and malignant pleural mesothelioma'. Together they form a unique fingerprint.

Cite this