FAK and paxillin, two potential targets in pancreatic cancer

Kanteti, Rajani; Batra, Surinder K.; Lennon, Frances E.; Salgia, Ravi

doi:10.18632/oncotarget.8040

Cited by 95 publications

(80 citation statements)

References 152 publications

(137 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…were validated by analyzing the expression of several rPaC-related proteins, including ITGA3, Src, FAK, and Rac. These proteins had been reported activated in the progression and metastasis of PaC (Kanteti, Batra, Lennon, & Salgia, 2016;Razidlo et al, 2015;Xu, Wang, An, & Xu, 2013), which also supported our results. And we further verified PaC cells transfected with ITGA2 and miR-107 inhibitors could stimulate the expression of those proteins.…”

Section: Discussionsupporting

confidence: 93%

Coexpression of UCA1 and ITGA2in pancreatic cancer cells target the expression of miR‐107 through focal adhesion pathway

Gong

et al. 2018

Journal Cellular Physiology

View full text Add to dashboard Cite

Objectives Abnormal expressions of microRNAs (miRNAs) are demonstrated in pancreatic cancer (PaC), but a major part of the mechanism remains elusive. This study mainly aimed to structure a coexpressed network of long noncoding RNA (lncRNA) and messenger RNA (mRNA) in PaC, as well as to explore their direct targets. Methods LncRNA and mRNA microarrays were used to determine the expression profiles in PaC cells. Analysis of Kyoto Encyclopedia of Genes and Genomes pathway was performed to identify pathways associated with differentially expressed mRNAs. Coexpression profiles were identified by constructing differentially expressed lncRNA‐mRNA regulatory network and further validated by quantitative real‐time polymerase chain reaction assay and western blot assay. The bioinformatics computational method was applied to predict the biological target of lncRNA and mRNA, which was identified by luciferase reporter assay. Migration/invasion ability and apoptosis rate of cells were assessed by transwell assay and flow cytometry assay. Results It was identified that the level of urothelial cancer associated 1 (UCA1) was increased in PaC cells, and the inhibition of UCA1 suppressed migration and invasion ability of the cancer cells. The luciferase reporter assay recognized that miR‐107 was targeted by UCA1, and integrin subunit α 2 (ITGA2) was further targeted by miR‐107. This confirmed the prediction of lncRNA‐miRNA‐mRNA regulation mechanism. In the regulatory pathways, UCA1 and ITGA2 promoted PaC progression via focal adhesion pathway related proteins such as ITGA3, SRC protooncogene/nonreceptor tyrosine kinase, protein tyrosine kinase 2, and AKT serine/threonine kinase 1. Conclusion The study revealed a regulatory network of UCA1‐miR‐107‐ITGA2 and validated UCA1 and ITGA2 as potential prognostic factors for PaC.

show abstract

Section: Discussionsupporting

confidence: 93%

Coexpression of UCA1 and ITGA2in pancreatic cancer cells target the expression of miR‐107 through focal adhesion pathway

Gong

et al. 2018

Journal Cellular Physiology

View full text Add to dashboard Cite

show abstract

“…Previous studies have revealed that FAK is a key molecule for cell proliferation, migration, and invasion during cancer progression . Focal adhesion kinase has also been shown to be upregulated in many cancers, including OS .…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have revealed that FAK is a key molecule for cell proliferation, migration, and invasion during cancer progression. (20)(21)(22)(23) Focal adhesion kinase has also been shown to be upregulated in many cancers, including OS. (13) Ren et al reported that p-FAK (Y397) was highly expressed in 37% of primary human OS tissues (42/113) and greater p-FAK (Y397) overexpression was associated with more aggressive OS and poor prognosis.…”

Section: Discussionmentioning

confidence: 99%

Antitumor effect of focal adhesion kinase inhibitor PF562271 against human osteosarcoma in vitro and in vivo

Wen

et al. 2017

Cancer Science

View full text Add to dashboard Cite

Focal adhesion kinase (FAK) overexpression is related to invasive and metastatic properties in different kinds of cancers. Target therapy by inhibiting FAK has achieved promising effect in some cancer treatments, but its effect in human osteosarcoma has not been well studied. In the present study, we analyzed the antitumor efficacy of PF562271, an FAK inhibitor, against osteosarcoma in vitro and in vivo. Phosphorylated FAK (Y397) was highly expressed in primary human osteosarcoma tumor samples and was associated with osteosarcoma prognosis and lung metastasis. PF562271 greatly suppressed proliferation and colony formation in human osteosarcoma cell lines. In addition, treatment of osteosarcoma cell lines with PF562271 induced apoptosis and downregulated the activity of the protein kinase B/mammalian target of rapamycin pathway. PF562271 also impaired the tube formation ability of endothelial cells in vitro. Finally, oral treatment with PF562271 in mice dramatically reduced tumor volume, weight, and angiogenesis of osteosarcoma xenografts in vivo. These results indicate that FAK inhibitor PF562271 can potentially be effectively used for the treatment of osteosarcoma.

show abstract

“…The prognosis of the patients with higher PAX expression was poorer than those with low expression of PAX [6]. PAX, which is an intracellular adaptor protein, plays a basic role in the organization of the cytoskeleton, this connects integrins to FAK and plays an important role in both the assembly and disassembly of focal adhesions [7]. Overexpression of FAK as well as overexpression of CD98 and β1 and β3 integrins was found to be associated with the progression of colon carcinoma and its liver metastases [8] while GPR56 was only just recently studied by Sewda et al [9] who have found that GPR56 expression was significantly correlated with the proximal tumor location and with the expression of mismatch repair genes.…”

Section: Introductionmentioning

confidence: 99%

The Percentage of Stained Cells is a More Reliable Parameter in Immunohistochemical Analysis than Scoring the Intensity of Staining: Expression of 9 Molecular Markers in Progression and Liver Metastases of Colorectal Cancer

Agrawal¹,

Agrawal²,

Łuc³

et al. 2017

JCT

View full text Add to dashboard Cite

Aims: Research for reliable molecular markers that provide prognostic and predictive information in colorectal cancer (CRC) is based on solid evidence that the staging system on its own cannot definitively predict the tumor behavior and guide clinical management of the disease. Methods and results: In this study we examined the immunohistochemical expression of 9 markers, namely membrane-bound mucin 1 (MUC1), paxillin (PAX), Focal Adhesion Kinase (FAK), G-protein coupled receptor 56 (GPR56), ORAI3 and well known markers of colon carcinoma microsatellite instability (MSI): MSH2, MSH6, MLH1 and PMS2 with respect to the percentage of stained cells and intensity score in colon carcinoma cells, both in the primary tumor and liver metastasis. We have related all of the mentioned markers with clinicopathological data, including the age of patients, grading of the primary tumor and TNM system. Western blotting assay was performed to identify the expression. Our present study showed that the evaluation of different markers with respect to intensity of staining and percentage of stained cancer cells may be considered as a prognostic marker for tumor progression and later for liver metastasis. This has been found for the percentage of stained cells particularly. 528colon cancer cells provides a more adequate method of immunohistochemical analysis than evaluation of the intensity of staining.

show abstract

FAK and paxillin, two potential targets in pancreatic cancer

Cited by 95 publications

References 152 publications

Coexpression of UCA1 and ITGA2in pancreatic cancer cells target the expression of miR‐107 through focal adhesion pathway

Coexpression of UCA1 and ITGA2in pancreatic cancer cells target the expression of miR‐107 through focal adhesion pathway

Antitumor effect of focal adhesion kinase inhibitor PF562271 against human osteosarcoma in vitro and in vivo

The Percentage of Stained Cells is a More Reliable Parameter in Immunohistochemical Analysis than Scoring the Intensity of Staining: Expression of 9 Molecular Markers in Progression and Liver Metastases of Colorectal Cancer

Contact Info

Product

Resources

About