IGFBP-rP1 suppresses epithelial–mesenchymal transition and metastasis in colorectal cancer

Zhu, Shuzhen; Zhang, J; Xu, Fangying; Xu, Enbo; Ruan, Wenjie; Ma, Yan; Huang, Qi; Lai, Maode

doi:10.1038/cddis.2015.59

Cited by 28 publications

(22 citation statements)

References 39 publications

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“…Established regulators of EMT, such as SNAI1 (SNAIL), FN1 (fibronectin), CDH2 (N-cadherin) and IGFBP3 (insulin-like growth factor binding protein 3) [ 38 , 39 ], were down-regulated by COX-1 knockdown. In contrast, the negative regulators of EMT promoting cell-cell adhesion, such as CDH1 (E-cadherin), EPCAM and OCLN (occludin) [ 38 ], and the IGFBP7 antagonist of IGFBPs [ 40 ], were significantly up-regulated in OV3/COX1KD cells (Figure 4A & 4B ).…”

Section: Resultsmentioning

confidence: 99%

Aberrant over-expression of COX-1 intersects multiple pro-tumorigenic pathways in high-grade serous ovarian cancer

et al. 2015

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Cyclooxygenase-1 (COX-1) is implicated in ovarian cancer. However, patterns of COX expression and function have been unclear and controversial. In this report, patterns of COX-1 and COX-2 gene expression were obtained from RNA-seq data through The Cancer Genome Atlas. Our analysis revealed markedly higher COX-1 mRNA expression than COX-2 in high-grade serous ovarian cancers (HGSOC) and higher COX-1 expression in HGSOC tumors than 10 other tumor types. High expression of COX-1 in HGSOC tumors was confirmed in an independent tissue microarray. In contrast, lower or similar expression of COX-1 compared to COX-2 was observed in endometrioid, mucinous and clear cell tumors. Stable COX-1 knockdown in HGSOC-representative OVCAR-3 ovarian cancer cells reduced gene expression in multiple pro-tumorigenic pathways. Functional cell viability, clonogenicity, and migration/invasion assays were consistent with transcriptomic changes. These effects were reversed by stable over-expression of COX-1 in SKOV-3 cells. Our results demonstrate a distinct pattern of COX-1 over-expression in HGSOC tumors and strong association of COX-1 with multiple pro-tumorigenic pathways in ovarian cancer cells. These findings provide additional insight into the role of COX-1 in human ovarian cancer and support further development of methods to selectively target COX-1 in the management of HGSOC tumors.

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Section: Resultsmentioning

confidence: 99%

Aberrant over-expression of COX-1 intersects multiple pro-tumorigenic pathways in high-grade serous ovarian cancer

et al. 2015

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“…Most importantly, a putative TGF-␤ target gene, IGFBP7, a novel tumor stroma marker of CAFs and endothelial cells, is also induced in the EMT-like phenotype of CRC cells [137]. Conversely, our laboratory first found that IGFBP7 could inhibit EMT and tumor metastasis by repressing TGF-beta-mediated EMT through the Smad signaling cascade in CRC cells [138]. IGFBP7 may have different roles in specific microenvironment.…”

Section: Microenvironmental Regulation Of Emtmentioning

confidence: 92%

Epithelial–mesenchymal transition in colorectal cancer metastasis: A system review

Cao

Liu

et al. 2015

Pathology - Research and Practice

317

240

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“…Further investigations showed that the knockdown of ASB3 promoted cell proliferation, migration, and invasion in cultured CRC cells, whereas the overexpression of WT ASB3 inhibited cell proliferation, migration, and invasion in vitro and reduced tumorigenicity and hepatic metastasis of CRC xenografts in vivo. Furthermore, we found that overexpression of ASB3 inhibited EMT of CRC cells, characterized by up-regulating epithelial markers β-catenin and E-cadherin and down-regulating mesenchymal markers TCF8, N-cadherin, and vimentin [43, 44]. Conclusively, ASB3 exerts a tumor-suppressive role in the pathogenesis and progression of CRC.…”

Section: Discussionmentioning

confidence: 99%

The loss-of-function mutations and down-regulated expression of ASB3 gene promote the growth and metastasis of colorectal cancer cells

Lü

et al. 2017

Chin J Cancer

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BackgroundAnkyrin repeat and SOCS box protein 3 (ASB3) is a member of ASB family and contains ankyrin repeat sequence and SOCS box domain. Previous studies indicated that it mediates the ubiquitination and degradation of tumor necrosis factor receptor 2 and is likely involved in inflammatory responses. However, its effects on oncogenesis are unclear. This study aimed to investigate the effects of ASB3 on the growth and metastasis of colorectal cancer (CRC).MethodsWe used next-generation sequencing or Sanger sequencing to detect ASB3 mutations in CRC specimens or cell lines, and used real-time quantitative polymerase chain reaction, Western blotting, and immunohistochemical or immunofluorescence assay to determine gene expression. We evaluated cell proliferation by MTT and colony formation assays, tested cell cycle distribution by flow cytometry, and assessed cell migration and invasion by transwell and wound healing assays. We also performed nude mouse experiments to evaluate tumorigenicity and hepatic metastasis potential of tumor cells.ResultsWe found that ASB3 gene was frequently mutated (5.3%) and down-regulated (70.4%) in CRC cases. Knockdown of endogenous ASB3 expression promoted CRC cell proliferation, migration, and invasion in vitro and facilitated tumorigenicity and hepatic metastasis in vivo. Conversely, the ectopic overexpression of wild-type ASB3, but not that of ASB3 mutants that occurred in clinical CRC tissues, inhibited tumor growth and metastasis. Further analysis showed that ASB3 inhibited CRC metastasis likely by retarding epithelial-mesenchymal transition, which was characterized by the up-regulation of β-catenin and E-cadherin and the down-regulation of transcription factor 8, N-cadherin, and vimentin.Conclusion ASB3 dysfunction resulted from gene mutations or down-regulated expression frequently exists in CRC and likely plays a key role in the pathogenesis and progression of CRC.

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IGFBP-rP1 suppresses epithelial–mesenchymal transition and metastasis in colorectal cancer

Cited by 28 publications

References 39 publications

Aberrant over-expression of COX-1 intersects multiple pro-tumorigenic pathways in high-grade serous ovarian cancer

Aberrant over-expression of COX-1 intersects multiple pro-tumorigenic pathways in high-grade serous ovarian cancer

Epithelial–mesenchymal transition in colorectal cancer metastasis: A system review

The loss-of-function mutations and down-regulated expression of ASB3 gene promote the growth and metastasis of colorectal cancer cells

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