Evaluation of the Role of ITGBL1 in Ovarian Cancer

Cortez, Alexander Jorge; Kujawa, Katarzyna Aleksandra; Wilk, Agata; Sojka, Damian Robert; Syrkis, Joanna Patrycja; Olbryt, Magdalena; Lisowska, Katarzyna

doi:10.3390/cancers12092676

Cited by 11 publications

(6 citation statements)

References 40 publications

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“…We found that ITGBL1 also has a good diagnostic effect (AUC = 0.84) for CAN. It is worth noting that IT-GBL1 can promote the migration of ovarian cancer and breast cancer through the WNT pathway [28,29]. The role of ITGBL1 in CAN has not been reported, which may be an important protein in pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Identification of Hub Gene and Transcription Factor Related to Chronic Allograft Nephropathy Based on WGCNA Analysis

Zhu

Tang

Peng

et al. 2022

Kidney Blood Press Res

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Introduction Kidney transplantation has surpassed dialysis as the optimal therapy for end-stage kidney disease (ESKD). Yet, most patients could suffer from a slow but continuous deterioration of kidney function leading to graft loss mostly due to chronic allograft nephropathy (CAN) after KT. The dysregulated gene expression for CAN is still poorly understood. Methods To explore the pathogenesis of genomics in CAN, we analyzed the differentially expressed genes (DEGs) of kidney transcriptome between CAN and non-rejecting patients by downloading gene expression microarrays from the Gene Expression Omnibus (GEO) database. Then, we used weighted gene co-expression network analysis (WGCNA) to analyze the co-expression of DEGs to explore key modules, hub genes, and transcription factors in CAN. Functional enrichment analysis of key modules was performed to explore pathogenesis. ROC curve analysis was used to validate hub genes. Results As a result, 3 key modules and 15 hub genes were identified by WGCNA analysis. 3 key modules had 21 mutual Gene Ontology (GO) term enrichment functions. Extracellular structure organization, extracellular matrix organization, and extracellular region were identified as significant functions in CAN. Furthermore, transcription factor 12 was identified as the key transcription factor regulating key modules. All 15 hub genes: Yip1 interacting factor homolog B, membrane trafficking protein(YIF1B), toll like receptor 8 (TLR8), neutrophil cytosolic factor 4 (NCF4), glutathione peroxidase 8 (GPX8), mesenteric estrogen dependent adipogenesis (MEDAG), decorin(DCN), serpin family F member 1 (SERPINF1), integrin subunit beta like 1 (ITGBL1), SRY-box transcription factor 15 (SOX15), trophinin associated protein (TROAP), SRY-box transcription factor 1 (SOX1), metallothionein 3 (MT3), lysosomal protein transmembrane (5LAPTM5), FERM domain containing kindlin 3 (FERMT3), cathepsin S (CTSS) had a great diagnostic performance (AUC>0.7). Conclusion This study updates information and provides a new perspective for understanding the pathogenesis of CAN by bioinformatics means. More research is needed to validate and explore the results we have found to reveal the mechanisms underlying CAN.

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Section: Discussionmentioning

confidence: 99%

Identification of Hub Gene and Transcription Factor Related to Chronic Allograft Nephropathy Based on WGCNA Analysis

Zhu

Tang

Peng

et al. 2022

Kidney Blood Press Res

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“…It encodes a secreted protein of 54 kD composed of 10 integrin-like EGF repeats with similarities to the extracellular domain of integrin β1 chain. In one ovarian cancer study, ITGBL1 was shown to associate with β1 integrins and reduce their activity (Cortez et al 2020 ). The mode of action for this secreted protein is still unclear, but it might affect the activation status of integrin heterodimers, which might also depend on the nature of the α chain present in the integrin heterodimer with which ITGBL is interacting.…”

Section: Tumor Fibrosismentioning

confidence: 99%

Integrin α11β1 in tumor fibrosis: more than just another cancer-associated fibroblast biomarker?

Zeltz

Navab

Heljasvaara

et al. 2022

J. Cell Commun. Signal.

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There is currently an increased interest in understanding the role of the tumor microenvironment (TME) in tumor growth and progression. In this context the role of integrins in cancer-associated fibroblasts (CAFs) will need to be carefully re-evaluated. Fibroblast-derived cells are not only in the focus in tumors, but also in tissue fibrosis as well as in inflammatory conditions. The recent transcriptional profiling of what has been called “the pan-fibroblast cell lineage” in mouse and human tissues has identified novel transcriptional biomarker mRNAs encoding the secreted ECM proteins dermatopontin and collagen XV as well as the phosphatidylinositol-anchored membrane protein Pi16. Some of the genes identified in these fibroblasts scRNA-seq datasets will be useful for rigorous comparative characterizations of fibroblast-derived cell subpopulations. At the same time, it will be a challenge in the coming years to validate these transcriptional mRNA datasets at the protein-(expression) and at tissue-(distribution) levels and to find useful protein biomarker reagents that will facilitate fibroblast profiling at the cell level. In the current review we will focus on the role of the collagen-binding integrin α11β1 in CAFs, summarizing our own work as well as published datasets with information on α11 mRNA expression in selected tumors. Our experimental data suggest that α11β1 is more than just another biomarker and that it as a functional collagen receptor in the TME is playing a central role in regulating collagen assembly and matrix remodeling, which in turn impact tumor growth and metastasis.

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“…Integrin beta‐like 1 (ITGBL1), encoding a protein comprising 10 integrin epidermal EGF‐like repeat domains, was initially isolated from a cDNA library derived from osteoblasts in 1999 10 . Prior research has indicated a correlation between ITGBL1 and the advancement and spread of several forms of cancer, including liver, 11 ovarian, 12 breast 13 and colorectal cancers 14 as well as GC 15 . Rongkun Li noted that the upregulated expression of ITGBL1 exhibited a favourable correlation with both the tumour‐node‐metastasis (TNM) stage and the occurrence of distant metastasis in GC patients 16 .…”

Section: Introductionmentioning

confidence: 99%

ITGBL1 promotes anoikis resistance and metastasis in human gastric cancer via the AKT/FBLN2 axis

Shen,

Xia,

Wang

et al. 2024

J Cellular Molecular Medi

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The resistance to anoikis plays a critical role in the metastatic progression of various types of malignancies, including gastric cancer (GC). Nevertheless, the precise mechanism behind anoikis resistance is not fully understood. Here, our primary focus was to examine the function and underlying molecular mechanism of Integrin beta‐like 1 (ITGBL1) in the modulation of anoikis resistance and metastasis in GC. The findings of our investigation have demonstrated that the overexpression of ITGBL1 significantly augmented the resistance of GC cells to anoikis and promoted their metastatic potential, while knockdown of ITGBL1 had a suppressive effect on both cellular processes in vitro and in vivo. Mechanistically, we proved that ITGBL1 has a role in enhancing the resistance of GC cells to anoikis and promoting metastasis through the AKT/Fibulin‐2 (FBLN2) axis. The inhibition of AKT/FBLN2 signalling was able to reverse the impact of ITGBL1 on the resistance of GC cells to anoikis and their metastatic capability. Moreover, the expression levels of ITGBL1 were found to be significantly elevated in the cancerous tissues of patients diagnosed with GC, and there was a strong correlation observed between high expression levels of ITGBL1 and worse prognosis among individuals diagnosed with GC. Significantly, it was revealed that within our cohort of GC patients, individuals exhibiting elevated ITGBL1 expression and diminished FBLN2 expression experienced the worst prognosis. In conclusion, the findings of our study indicate that ITGBL1 may serve as a possible modulator of resistance to anoikis and the metastatic process in GC.

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Evaluation of the Role of ITGBL1 in Ovarian Cancer

Cited by 11 publications

References 40 publications

Identification of Hub Gene and Transcription Factor Related to Chronic Allograft Nephropathy Based on WGCNA Analysis

Identification of Hub Gene and Transcription Factor Related to Chronic Allograft Nephropathy Based on WGCNA Analysis

Integrin α11β1 in tumor fibrosis: more than just another cancer-associated fibroblast biomarker?

ITGBL1 promotes anoikis resistance and metastasis in human gastric cancer via the AKT/FBLN2 axis

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