Asporin participates in gastric cancer cell growth and migration by influencing EGF receptor signaling

Ding, Qian; Zhang, Mei; Liu, Can

doi:10.3892/or.2015.3791

Cited by 28 publications

(39 citation statements)

References 39 publications

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“…In addition to ADAMTS , ADAM12 , COMP and CTHRC1 , we identified asporin ( ASPN ) and Wnt1-inducible-signaling pathway protein 1 ( WISP1 ) as upregulated in both centre and margin Kd, which are also correlated with TGF β expression. ASPN , a small leucine-rich proteoglycan though to regulate tumour microenvironment, is known to bind TGF β [96, 97] and has previously been found to be upregulated in the margin of KD [98]. The pro-proliferative WISP1 , a member of the matricellular CCN family, was detected in Dupuytren’s disease [99] and is strongly associated with liver [100] and lung fibrosis, where it was induced by TGF β1 [101] and implicated in EMT.…”

Section: Resultsmentioning

confidence: 99%

Site-specific gene expression profiling as a novel strategy for unravelling keloid disease pathobiology

et al. 2017

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Keloid disease (KD) is a fibroproliferative cutaneous tumour characterised by heterogeneity, excess collagen deposition and aggressive local invasion. Lack of a validated animal model and resistance to a multitude of current therapies has resulted in unsatisfactory clinical outcomes of KD management. In order to address KD from a new perspective, we applied for the first time a site-specific in situ microdissection and gene expression profiling approach, through combined laser capture microdissection and transcriptomic array. The aim here was to analyse the utility of this approach compared with established methods of investigation, including whole tissue biopsy and monolayer cell culture techniques. This study was designed to approach KD from a hypothesis-free and compartment-specific angle, using state-of-the-art microdissection and gene expression profiling technology. We sought to characterise expression differences between specific keloid lesional sites and elucidate potential contributions of significantly dysregulated genes to mechanisms underlying keloid pathobiology, thus informing future explorative research into KD. Here, we highlight the advantages of our in situ microdissection strategy in generating expression data with improved sensitivity and accuracy over traditional methods. This methodological approach supports an active role for the epidermis in the pathogenesis of KD through identification of genes and upstream regulators implicated in epithelial-mesenchymal transition, inflammation and immune modulation. We describe dermal expression patterns crucial to collagen deposition that are associated with TGFβ-mediated signalling, which have not previously been examined in KD. Additionally, this study supports the previously proposed presence of a cancer-like stem cell population in KD and explores the possible contribution of gene dysregulation to the resistance of KD to conventional therapy. Through this innovative in situ microdissection gene profiling approach, we provide better-defined gene signatures of distinct KD regions, thereby addressing KD heterogeneity, facilitating differential diagnosis with other cutaneous fibroses via transcriptional fingerprinting, and highlighting key areas for future KD research.

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Section: Resultsmentioning

confidence: 99%

Site-specific gene expression profiling as a novel strategy for unravelling keloid disease pathobiology

et al. 2017

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“…Interestingly, Hs578T and SNB-75 cancer cells with asporin expression have the highest expression of smooth muscle actin (Supplementary Figure S1B). Asporin has also been reported to be expressed by gastric cancer cell lines and to enhance their oncogenic properties [42]. As asporin belongs to secreted proteins, regulation of its expression both in CAFs and cancer cell is relevant for alteration of the tumor microenvironment.…”

Section: Discussionmentioning

confidence: 99%

The dual role of asporin in breast cancer progression

et al. 2016

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Asporin has been reported as a tumor suppressor in breast cancer, while asporin-activated invasion has been described in gastric cancer. According to our in silico search, high asporin expresion associates with significantly better relapse free survival (RFS) in patients with low-grade tumors but RFS is significantly worse in patients with grade 3 tumors. In line with other studies, we have confirmed asporin expression by RNA scope in situ hybridization in cancer associated fibroblasts. We have also found asporin expression in the Hs578T breast cancer cell line which we confirmed by quantitative RT-PCR and western blotting. From multiple testing, we found that asporin can be downregulated by bone morphogenetic protein 4 while upregulation may be facilited by serum-free cultivation or by three dimensional growth in stiff Alvetex scaffold. Downregulation by shRNA inhibited invasion of Hs578T as well as of CAFs and T47D cells. Invasion of asporin-negative MDA-MB-231 and BT549 breast cancer cells through collagen type I was enhanced by recombinant asporin. Besides other investigations, large scale analysis of aspartic acid repeat polymorphism will be needed for clarification of the asporin dual role in progression of breast cancer.

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“…Previously studies indicated that asporin might inhibit the TGF-β1 [17] and bone morphogenetic protein 2 (BMP-2) signaling pathways [8]. In gastric cancer, asporin contributes to metastasis through EGFR and ERK-CD44/MMP-2 pathways [9]. Awata et al demonstrated that asporin could directly bind to FGF-2 and form an FGF-2–FGFR1 complex [18].…”

Section: Discussionmentioning

confidence: 99%

“…It was firstly identified in human cartilage [5] and it was associated with the pathogenesis of bone and joint diseases, including osteoarthritis [6], intervertebral disc degeneration [7] and periodontal ligament mineralization [8]. Recently, asporin was found to play important roles in gastric cancer [9, 10], pancreatic cancer [11, 12] and prostate cancer [13]. However, whether asporin is involved in the CRC development and progression has not been clarified.…”

Section: Introductionmentioning

confidence: 99%

Asporin enhances colorectal cancer metastasis through activating the EGFR/Src/cortactin signaling pathway

Jing

Cheng

et al. 2016

Oncotarget

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Asporin has been implicated as an oncogene in various types of human cancers; however, the roles of asporin in the development and progression of colorectal cancer (CRC) have not yet been determined. With clinical samples, we found that asporin was highly expressed in CRC tissues compared to adjacent normal tissues and the asporin expression levels were significantly associated with lymph node metastasis status and TNM stage of the patients. Through knockdown of asporin in CRC cell lines RKO and SW620 or overexpression of asporin in cell lines HT-29 and LoVo, we found that asporin could enhance wound healing, migration and invasion abilities of the CRC cells. Further more, with the human umbilical vein endothelial cells (HUVECs) tube formation assays and the xenograft model, we found that asporin promoted the tumor growth through stimulating the VEGF signaling pathway. The portal vein injection models suggested that asporin overexpression stimulated the liver metastasis of HT29 cell line, while asporin knockdown inhibited the liver metastasis of RKO cell line. In addition, asporin was found to augment the phosphorylation of EGFR/Src/cortactin signaling pathway, which might be contributed to the biological functions of asporin in CRC metastasis. These results suggested that asporin promoted the tumor growth and metastasis of CRC, and it could be a potential therapeutic target for CRC patients in future.

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Asporin participates in gastric cancer cell growth and migration by influencing EGF receptor signaling

Cited by 28 publications

References 39 publications

Site-specific gene expression profiling as a novel strategy for unravelling keloid disease pathobiology

Site-specific gene expression profiling as a novel strategy for unravelling keloid disease pathobiology

The dual role of asporin in breast cancer progression

Asporin enhances colorectal cancer metastasis through activating the EGFR/Src/cortactin signaling pathway

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