The small molecule compound Y15 and PF04554878 in TT cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Dan Wang
PROVIDER: E-GEOD-55619 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Purpose: Focal adhesion kinase (FAK), hyaluronan (HA), and hyaluronan synthase-3 (HAS3) have been implicated in cancer growth and progression. FAK inhibition with the small molecule inhibitor Y15 decreases colon cancer cell growth in vitro and in vivo. HAS3 inhibition in colon cancer cells decreases FAK expression and activation, and exogenous HA increases FAK activation. We sought to determine the genes affected by HAS and FAK inhibition and hypothesized that dual inhibition would synergistically inhibit viability. Methods: We treated SW620 colon cancer cells with Y15 to inhibit FAK. We used two strategies to inhibit HAS: (1) cells were transfected with siRNA (HAS3 inhibited); a scrambled sequence was used as a control (HAS3 scrambled), and (2) cells were treated with the HAS inhibitor 4-methylumbelliferone (4-MU). To determine the effect on viability, MTT assays were performed on transfected cells treated with Y15, and wild type cells treated with Y15 alone, 4-MU alone or Y15+4-MU. Treated and untreated cells were submitted to the gene microarray facility for expression profiling. RT-PCR was done to confirm the results. Results: HAS and FAK inhibition affected cell viability. Y15 and 4-MU decreased viability in a dose-dependent manner; viability was further inhibited by treatment with Y15+4-MU in combination (p<0.05). HAS-inhibited cells treated with as little as 2 M of Y15 showed significantly decreased viability compared to HAS scrambled cells treated with the same dose (p<0.05), suggesting synergistic inhibition of viability with dual FAK/HAS inhibition. Microarray analysis showed more than 2-fold up- or down-regulation of 121 genes by HAS inhibition, and 696 genes by FAK inhibition (p<0.05). Of 29 genes that were common to both groups, 9 were down-regulated (CBS, DHRS3, EEPD1, ESPN, FAM46C, GRTP1, IL20RA, INHBE, SCNN1A) and 4 were up-regulated (ANXA1, MALL, RGS2, SNAI2). RT-PCR confirmed these findings. Among the genes affected by FAK or HAS3 inhibition were FOX genes (apoptosis, cell cycle regulation), ANXA1 (apoptosis, proliferation), IL8 (cell cycle regulation, adhesion, proliferation), RGS2 (cell cycle regulation), CEACAM6 (adhesion), SNAI2 (transcription regulation), and SFRP5 (apoptosis). Several genes were specific to either FAK or HAS3 inhibition and several were common to both. Gene expression profiles of samples isolated from human colorectal cancer cells (SW620). A comparison of gene expression between untreated cells and cells treated with 4mcM of Y15. A second comparison between cells transfected with siRNA to HAS3 (HAS3-silenced) and cells transfected with a scrambled control sequence (sc). Two replicates each.
2013-06-01 | E-GEOD-39168 | biostudies-arrayexpress
Project description:The gene expression profiles were identified in glioblastoma cells treated with FAK inhibitor Y15, temozolomide alone or with combination of Y15 and Temozolomide DBTRG and U87 were treated with FAK inhibitor Y15 at 10 microM for 24 h; U87 cells were treated with Temozolomide 100 microM for 24 h and Y15+temozolomide at the same dose as each agent alone
2013-01-12 | E-GEOD-43452 | biostudies-arrayexpress
Project description:Global gene expression in TT cells treated with FAK inhibitors
2015-07-03 | GSE55619 | GEO
Project description:3 papillary thyroid cancer cell lines were compared, treated with Y15 to untreated. 1 million cells of each papillary thyroid cell line (TPC1, K1, BCPAP) were plated, treated 24 hours later with 10uM Y15, and collected 24 hours later by trypsinization.
2014-03-06 | E-GEOD-55603 | biostudies-arrayexpress
Project description:The gene expression profiles were identified in glioblastoma cells treated with FAK inhibitor Y15, temozolomide alone or with combination of Y15 and Temozolomide
2013-01-12 | GSE43452 | GEO
Project description:Purpose: Focal adhesion kinase (FAK), hyaluronan (HA), and hyaluronan synthase-3 (HAS3) have been implicated in cancer growth and progression. FAK inhibition with the small molecule inhibitor Y15 decreases colon cancer cell growth in vitro and in vivo. HAS3 inhibition in colon cancer cells decreases FAK expression and activation, and exogenous HA increases FAK activation. We sought to determine the genes affected by HAS and FAK inhibition and hypothesized that dual inhibition would synergistically inhibit viability. Methods: We treated SW620 colon cancer cells with Y15 to inhibit FAK. We used two strategies to inhibit HAS: (1) cells were transfected with siRNA (HAS3 inhibited); a scrambled sequence was used as a control (HAS3 scrambled), and (2) cells were treated with the HAS inhibitor 4-methylumbelliferone (4-MU). To determine the effect on viability, MTT assays were performed on transfected cells treated with Y15, and wild type cells treated with Y15 alone, 4-MU alone or Y15+4-MU. Treated and untreated cells were submitted to the gene microarray facility for expression profiling. RT-PCR was done to confirm the results. Results: HAS and FAK inhibition affected cell viability. Y15 and 4-MU decreased viability in a dose-dependent manner; viability was further inhibited by treatment with Y15+4-MU in combination (p<0.05). HAS-inhibited cells treated with as little as 2 M of Y15 showed significantly decreased viability compared to HAS scrambled cells treated with the same dose (p<0.05), suggesting synergistic inhibition of viability with dual FAK/HAS inhibition. Microarray analysis showed more than 2-fold up- or down-regulation of 121 genes by HAS inhibition, and 696 genes by FAK inhibition (p<0.05). Of 29 genes that were common to both groups, 9 were down-regulated (CBS, DHRS3, EEPD1, ESPN, FAM46C, GRTP1, IL20RA, INHBE, SCNN1A) and 4 were up-regulated (ANXA1, MALL, RGS2, SNAI2). RT-PCR confirmed these findings. Among the genes affected by FAK or HAS3 inhibition were FOX genes (apoptosis, cell cycle regulation), ANXA1 (apoptosis, proliferation), IL8 (cell cycle regulation, adhesion, proliferation), RGS2 (cell cycle regulation), CEACAM6 (adhesion), SNAI2 (transcription regulation), and SFRP5 (apoptosis). Several genes were specific to either FAK or HAS3 inhibition and several were common to both.
2013-06-01 | GSE39168 | GEO
Project description:Global gene expression in HCT116p53-/- and HCT116p53+/+ cells HCT116p53-/- and p53+/+ were untreated and treated with P2 small molecule compound at 25 microM, total RNA was isolated and gene expression was analyzed using Illumina chips
2012-11-23 | E-GEOD-33918 | biostudies-arrayexpress
Project description:To explore the potential role of focal adhesion kinase (FAK) in trophoblast functions in early-onset preeclampsia (EOPE).We first examined expression and localization in placental tissue as well as in villus tissue during early pregnancy. Then, FAK activity was inhibited with Y15. The effects of FAK on the invasion and proliferation of trophoblast cells (HTR8/SVneo) were investigated. Transcriptomic and bioinformatics analyses were then used to predict the possible pathways by which FAK is involved in PE. Finally, we measured the expression of FAK in a PE mouse model. Transcriptomic and bioinformatics results suggest that Rap1 may be a downstream regulator of trophoblast FAK. In mouse models, we found reduced expression of FAK and Rap1 in the placenta of PE mice.
2025-07-10 | GSE271940 | GEO
Project description:A large portion of the genome is transcribed but many of the resulting RNAs live only transiently and can generally not be mapped. Here we develop transient transcriptome sequencing (TT-Seq), a protocol that maps transcriptionally active regions in a nearly uniform manner and allows for unbiased monitoring of cellular RNA synthesis activity. Application of TT-Seq to human K562 cells recovers stable mRNAs and long intergenic non-coding RNAs, and additionally maps over 10,000 transient RNAs including enhancer RNAs, antisense RNAs, promoter-associated upstream antisense and convergent RNAs. TT-Seq also provides RNA half-lives, and reveals that transient RNAs are short and lack U1 motifs and secondary structure. TT-Seq further uncovers transcription termination sites and reveals a universal DNA motif for RNA polymerase II release.
2016-06-03 | GSE75792 | GEO