IGFBP3, a Transcriptional Target of Homeobox D10, Is Correlated with the Prognosis of Gastric Cancer

Xue, Min; Fang, Yanfei; Sun, Guozhe; Zhuo, Wei; Zhong, Jing; Qian, Cheng; Wang, Lan; Wang, Liangjing; Si, Jianmin; Chen, Shujie

doi:10.1371/journal.pone.0081423

Cited by 37 publications

(33 citation statements)

References 43 publications

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“…The downregulation of IGFBP3 we observed is consistent with reported roles as a suppressor of cell migration, tumor progression and metastasis for prostate, colorectal, gastric and endometrial cancers [32][33][34][35][36]. The type 1 insulin-like growth factor receptor (IGF1R) is overexpressed in prostate cancer (PCa; [37]) and its function in the PC3M parental cell line, PC3, is well documented, suggesting that HGF-induced IGF1BP3 downregulation in PC3M would most likely increase IGF1R responsiveness to available IGF1, and in turn enhance cell survival, proliferation and motility.…”

Section: Analysis Of Hgf Motogenic Signaling By Gene Expression Profisupporting

confidence: 91%

Expression array analysis of the hepatocyte growth factor invasive program

Cecchi

Lih

Lee

et al. 2015

Clin Exp Metastasis

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Signaling by human hepatocyte growth factor (hHGF) via its cell surface receptor (MET) drives mitogenesis, motogenesis and morphogenesis in a wide spectrum of target cell types and embryologic, developmental and homeostatic contexts. Oncogenic pathway activation also contributes to tumorigenesis and cancer progression, including tumor angiogenesis and metastasis, in several prevalent malignancies. The HGF gene encodes full-length hHGF and two truncated isoforms known as NK1 and NK2. NK1 induces all three HGF activities at modestly reduced potency, whereas NK2 stimulates only motogenesis and enhances HGF-driven tumor metastasis in transgenic mice. Prior studies have shown that mouse HGF (mHGF) also binds with high affinity to human MET. Here we show that, like NK2, mHGF stimulates cell motility, invasion and spontaneous metastasis of PC3M human prostate adenocarcinoma cells in mice through human MET. To identify target genes and signaling pathways associated with motogenic and metastatic HGF signaling, i.e., the HGF invasive program, gene expression profiling was performed using PC3M cells treated with hHGF, NK2 or mHGF. Results obtained using Ingenuity Pathway Analysis software showed significant overlap with networks and pathways involved in cell movement and metastasis. Interrogating The Cancer Genome Atlas project also identified a subset of 23 gene expression changes in PC3M with a strong tendency for co-occurrence in prostate cancer patients that were associated with significantly decreased disease-free survival.

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Section: Analysis Of Hgf Motogenic Signaling By Gene Expression Profisupporting

confidence: 91%

Expression array analysis of the hepatocyte growth factor invasive program

Cecchi

Lih

Lee

et al. 2015

Clin Exp Metastasis

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“…Nevertheless, it is too soon to exclude local IGFBP3 protein expression from being a biomarker. In gastric cancer, IGFBP3 deficiency in IHC was found to be correlated with advanced lymph node stage and poor survival (39). It is still necessary and promising to probe the relationship of local IGFBP3 expression with other clinicopathological factors and CRC patient prognosis in a larger cohort with mature survival data.…”

Section: Discussionmentioning

confidence: 99%

miR‑197 promotes the invasion and migration of colorectal cancer by targeting insulin‑like growth factor‑binding protein�3

Zhou

Sun

et al. 2018

Oncol Rep

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The incidence and mortality of colorectal cancer (CRC) have been rising rapidly in China. A number of miRNAs have been confirmed to be involved in diverse biological processes of CRC. However, whether miR‑197 plays a role in migration and invasion of CRC has never been explored. In the present study Transwell chambers were used in in vitro migration and invasion assays. Dual-luciferase reporter assay was employed to confirm the target of miR‑197. RT‑PCR and IHC staining were performed to quantify miR‑197 and IGFBP3 expression, respectively. Clinicopathological features were collected for statistical analysis. We observed that the overexpression of miR‑197 significantly promoted migration and invasion in 3 CRC cell lines including HCT8, HCT116 and SW480 (P<0.05), while the inhibition of miR‑197 weakened both biological processes (P<0.05). In bioinformatics and dual-luciferase reporter assay, luciferase activities of IGFBP3‑WT‑transfected cells significantly decreased upon miR‑197 overexpression and this inhibitory effect was abolished when miR‑197 binding region in IGFBP3 3'‑UTR was mutated, which indicated that miR‑197 directly suppressed the expression of IGFBP3 in CRC cells by targeting its 3'UTR. Downregulation of the expression of IGFBP3 by using targeted siRNA led to significant enhancement of cell migration and invasion in two CRC cell lines including HCT8 and HCT116 (P<0.05). Finally, in cancerous tissues of CRC patients, the miR‑197 level was inversely correlated with the expression of IGFBP3 (P=0.026), which indicated that miR‑197 may modulate cell migration and invasion by targeting IGFBP3 in CRC patients. In conclusion, we revealed that miR‑197 modulates IGFBP3 and therefore plays a critical role in regulating CRC migration and invasion.

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“…Furthermore, Xue and collagus also indicated that IGFBP-3 can suppres some invasion factor like urokinase-type plasminogen activator (uPA) and MMP-14 (35). Harada and colleagues also showed that IGFBP-3 can induce apoptosis via IGFBP-3R in lung cancer (36).…”

Section: Discussionmentioning

confidence: 99%

Decreased expression of Insulin-like growth factor binding protein 3 and its death receptor in association with poor prognosis of the patients with gastric cancer

Ansari¹,

Gheysarzadeh²,

Bakhtiari³

et al. 2020

Preprint

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Background: Gastric cancer (GC) as one of the most common cancers, serves as the third cause of cancer-related death. Insulin-like growth factor binding protein 3 (IGFBP-3) and its novel death receptor (IGFBP-3R) has been shown to have an anti-tumor effect however their prognostic values have not been elucidated yet. Methods: IGFBP-3 and IGFBP-3R expression were evaluated with quantitative real-time polymerase chain reaction and western blotting in patients with GC (N=68). The relationship between prognostic factors such as tumor stage, tumor grade, tumor size, metastases, and Overall Survival (OS) with IGFBP-3/IGFBP-3R expression was also assessed. Results: IGFBP-3 and its death receptor expression were determined as dialectic evidence. In the experimental procedure, IGFBP-3 and IGFBP-3R expression were reduced in tumor tissues significantly. We found that there was an association between the reduction of IGFBP-3 with lymph node metastasis and TMN staging ( P<0.001 ). In addition, IGFBP-3R expression was associated with tumor size ( P=0.004 ), lymph node metastasis ( P<0.001 ), differentiation ( P=0.002 ) and TNM classification ( P=0.005 ). Interestingly, we presented that the downregulation of IGFBP-3R was stage-dependent. In OS analysis, we offered that low levels of IGFBP-3R mRNA expression were unfavorable with survival rate (P=0.002 ). IGFBP-3 regardless of its relationship with some prognostic parameters, there was no significant relationship between IGFBP-3 and OS. Conclusion: The findings of this study showed that IGFBP-3R has the potential to be a new prognostic biomarker of GC. But despite some benefit of IGFBP-3, it cannot be accepted as a prognostic biomarker. However, this finding must be improved and confirmed by future studies.

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IGFBP3, a Transcriptional Target of Homeobox D10, Is Correlated with the Prognosis of Gastric Cancer

Cited by 37 publications

References 43 publications

Expression array analysis of the hepatocyte growth factor invasive program

Expression array analysis of the hepatocyte growth factor invasive program

miR‑197 promotes the invasion and migration of colorectal cancer by targeting insulin‑like growth factor‑binding protein�3

Decreased expression of Insulin-like growth factor binding protein 3 and its death receptor in association with poor prognosis of the patients with gastric cancer

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