Introduction/Background Integrin beta-like 1 (ITGBL1) is a poorly characterized protein comprised of ten EGF-like repeats. Our previous studies suggested that higher ITGBL1 mRNA expression level in the tumor is related with shorter survival of ovarian cancer patients.1 2 Subsequent functional in vitro studies revealed that ITGBL1 overexpression in ovarian cancer cells resulted in the altered adhesion, migration and invasiveness, while it had no effect on proliferation rate and the cell cycle. ITGBL1-overexpressing cells were significantly more resistant to cisplatin and paclitaxel,3 major drugs used in OC treatment.4 In the current study we analyzed gene expression profiles of ITGBL1-overexpressing and control ovarian cancer cells and investigated ITGBL1 influence on ovarian cancer cell signaling pathways.
Methodology ITGBL1 coding sequence was PCR-amplified from cDNA and cloned into pLNCX2 vector. Retroviral system was used to obtain two ovarian cancer cell lines: OAW42/ITGBL1(+) and SKOV3/ITGBL1(+) with overexpression of ITGBL1. Control cell lines were obtained by transduction with an empty vector. RNA was isolated from wild type, ITGBL1-overexpressing and control cells. DNA microarray experiment was performed using GeneChip™ Human Transcriptome Array 2.0 (Affymetrix, Santa Clara, CA, USA) according to the manufacturer’s instructions. Bioinformatical analysis was carried out in R environment (version 3.5.3) with Bioconductor packages.
Results Using Principal Component Analysis, an unsupervised method of data analysis, we selected gene sets related to major sources of variability in our dataset. Then, by performing Gene Set Enrichment Analysis we found 76 and 146 significantly affected cellular signaling pathways (in OAW42 and SKOV3 cell line, respectively). Majority of them (22 and 44, respectively) were related to extracellular matrix structure and function, integrin signaling, focal adhesion, cell junction, cellular motility, ERBB2 and ERBB4 signaling, etc.
Conclusion Global gene expression analysis revealed that signaling pathways affected by ITGBL1 overexpression were mostly those related to extracellular matrix organization and function, integrin signaling, focal adhesion, cellular communication and motility. These results are concordant with functional changes observed in ITGBL1-overexpressing cells, like altered adhesiveness, enhanced motility and invasiveness. Overall, our results indicate that higher expression of ITGBL1 in ovarian cancer cells is associated with features that may worsen clinical course of the disease.
A.J.Cortez was co-financed by the EU through the European Social Fund (grant-POWR.03.02.00-00-I029).
Lisowska, et al. (2014), DOI:10.3389/fonc.2014.00006
Lisowska, et al. (2016), DOI:10.1007/s00432-016-2147-y
Cortez, et al. (2020), DOI: 10.3390/cancers12092676
Cortez, et al. (2020), DOI: 10.1007/s00280-017-3501-8
Disclosures Authors have nothing to disclose.
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