Upregulation of ITGBL1 predicts poor prognosis and promotes chemoresistance in ovarian cancer

Song, Jiandong; Yang, Pengxia; Lu, Jianjun

doi:10.3233/cbm-190460

Cited by 11 publications

(13 citation statements)

References 33 publications

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“…We also observed slightly increased in-vitro chemoresistance in ITGBL1-overexpressing cells; this may be explained only by more efficient ECM proteins deposition providing physical barrier for drug diffusion [ 35 , 36 ], since no classical pathways related with chemoresistance were found in our analysis. Of note, Song et al [ 25 ] also showed that ITGBL1 confers in-vitro resistance to cisplatin and paclitaxel, as well as in-vivo resistance to cisplatin (paclitaxel not tested). From among cell lines tested, only SKOV3 were overlapping with our experiment; interestingly, Song et al [ 25 ] observed much higher IC50 values for cisplatin than we did, and much greater difference in IC50 between control and ITGBL1-overexpressing SKOV3 cells.…”

Section: Discussionmentioning

confidence: 99%

“…Of note, Song et al [ 25 ] also showed that ITGBL1 confers in-vitro resistance to cisplatin and paclitaxel, as well as in-vivo resistance to cisplatin (paclitaxel not tested). From among cell lines tested, only SKOV3 were overlapping with our experiment; interestingly, Song et al [ 25 ] observed much higher IC50 values for cisplatin than we did, and much greater difference in IC50 between control and ITGBL1-overexpressing SKOV3 cells.…”

Section: Discussionmentioning

confidence: 99%

“…We were the first to report in 2013 that ITGBL1 overexpression stimulates ovarian cancer cell migration rate [ 12 ]. Later, since 2015, there have arisen a dozen or so reports concerning the ITGBL1 role in several human diseases, e.g., breast cancer [ 13 ], non-small cell lung cancer (NSCLC) [ 14 , 15 ], HBV-related liver pathologies [ 16 , 17 ], pulmonary fibrosis [ 15 ], osteoarthritis [ 18 ], colorectal [ 19 , 20 , 21 ], gastric [ 22 ], prostate [ 23 ] and ovarian cancer [ 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

“…In liver [ 16 , 17 ] and pulmonary [ 15 ] pathologies, higher expression of ITGBL1 was found to be correlated with severity of disease and its more advanced stage. Also, in the majority of solid tumors that were studied, a higher expression of ITGBL1 was found to be associated with a more advanced stage, with the presence of distant metastases, worse prognosis, and/or with chemoresistance, indicating oncogenic properties of ITGBL1 [ 13 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ]. The exception is NSCLC, in which ITGBL1 is postulated to play an opposite role of tumor suppressor, and its decreased level is associated with worse disease course [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of the Role of ITGBL1 in Ovarian Cancer

Cortez

Kujawa

Wilk

et al. 2020

Cancers

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In our previous microarray study we identified two subgroups of high-grade serous ovarian cancers with distinct gene expression and survival. Among differentially expressed genes was an Integrin beta-like 1 (ITGBL1), coding for a poorly characterized protein comprised of ten EGF-like repeats. Here, we have analyzed the influence of ITGBL1 on the phenotype of ovarian cancer (OC) cells. We analyzed expression of four putative ITGBL1 mRNA isoforms in five OC cell lines. OAW42 and SKOV3, having the lowest level of any ITGBL1 mRNA, were chosen to produce ITGBL1-overexpressing variants. In these cells, abundant ITGBL1 mRNA expression could be detected by RT-PCR. Immunodetection was successful only in the culture media, suggesting that ITGBL1 is efficiently secreted. We found that ITGBL1 overexpression affected cellular 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, major drugs used in OC treatment. 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 were consistent with the findings of our functional studies. Overall, our results indicate that higher expression of ITGBL1 in OC is associated with features that may worsen clinical course of the disease.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Evaluation of the Role of ITGBL1 in Ovarian Cancer

Cortez

Kujawa

Wilk

et al. 2020

Cancers

View full text Add to dashboard Cite

show abstract

“…Recently, studies on ITGBL1 have been increasing, and it was reported that ITGBL1 could promote bone metastasis of breast cancer through transforming growth factor (TGF)-β signaling pathway (1). Studies showed that ITGBL1 could promote the invasion of ovarian cancer cell through Wnt/planar cell polarity (PCP) signaling and focal adhesion kinase (FAK)/Src pathway (2), and high expression of ITGBL1 was related to the poor prognosis and drug resistance of ovarian cancer (3). In gastric cancer, ITGBL1 was linked to epithelial-mesenchymal transition (EMT) phenotype and poor prognosis (4).…”

Section: Introductionmentioning

confidence: 99%

Regulatory Mechanism of ITGBL1 in the Metastasis of Colorectal Cancer

2020

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Integrin, beta-like 1 (ITGBL1) protein is located in the extracellular matrix (ECM) and involved in the development and metastasis of many tumors. However, the regulatory mechanism of ITGBL1 in colorectal cancer (CRC) remains unclear. This study was to analyze the expression profile of CRC and to identify the expression change of ITGBL1 gene at different stages of CRC. Survival analysis showed that ITGBL1 was related to the metastasis of CRC, and CRC patients with a high expression of ITGBL1 had earlier metastasis. Gene Set Enrichment Analysis (GSEA) indicated the relationship between ITGBL1 expression and molecular events of CRC. The results indicated that a high expression of ITGBL1 was linked to Wnt signaling pathway, cell polarity, and tissue development, while a low expression of ITGBL1 was related to cellular respiration, electron transfer chain, and oxidative phosphorylation. With the expression profiles from interstitial and parenchyma CRC tissues, a comparison was made to determine the difference between high/low expression of ITGBL1 and Wnt signaling pathway, respectively, and further confirmed the close relation between ITGBL1 and Wnt signaling pathway. To determine the relation, an interaction network of ITGBL1 and Wnt signaling proteins was constructed. It was found that β-catenin interacted with multiple extracellular Wnt signals and could bind to ITGBL1. As a result, the regulatory mechanism of ITGBL1 in CRC is related to extracellular Wnt signals and may affect extracellular Wnt signals via β-catenin.

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