CDCP1 enhances Wnt signaling in colorectal cancer promoting nuclear localization of β-catenin and E-cadherin

He, Yaowu; Davies, Claire; Harrington, Brittney S.; Hellmers, Linh; Sheng, Yonghua; Broomfield, Amy; McGann, Thomas; Bastick, Kate; Zhong, Laurie; Wu, Alex; Maresh, Grace A.; McChesney, Shannon L.; Wong, Kuan Yau; Adams, Mark N.; Sullivan, Ryan C.; Palmer, Jodie; Burke, Les J.; Ewing, Adam D.; Zhang, Xin; Margolin, David A.; Li, Li; Lourie, Rohan; Matsika, Admire; Srinivasan, Bhuvana; McGuckin, Michael A.; Lumley, John W.; Hooper, John D.

doi:10.1038/s41388-019-0983-3

Cited by 33 publications

(24 citation statements)

References 47 publications

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“…16 Consistently, CDCP1 was found to be involved in the translocation of E-cadherin, and down-regulation of CDCP1 reduces nuclear localized E-cadherin, increases sequestration of this protein in cell membranes and reduces CRC tumor burden. 11 On the basis of the above results, we come to a conclusion that CDCP1 might promote cell migration and invasion partially by facilitating the EMT process.…”

Section: Discussionmentioning

confidence: 77%

“…CDCP1 plays a role in the tyrosine phosphorylation-dependent regulation of cellular events that are involved in tumor invasion and metastasis. 5,6 Emerging evidence have revealed significant contributions of CDCP1 in tumorigenesis, including colon, [7][8][9][10][11] renal, 12,13 ovarian, 14,15 pancreatic, 16,17 prostate 18 and breast 19,20 cancers. Furthermore, elevated expression of CDCP1 correlates with poor outcome in renal, 13 lung, 21 colon, 10 pancreatic 17 and ovarian 14 cancers.…”

Section: Introductionmentioning

confidence: 99%

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<p>CUB Domain-Containing Protein-1 Promotes Proliferation, Migration and Invasion in Cervical Cancer Cells</p>

Huang¹,

Chen²,

Lai³

et al. 2020

CMAR

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Emerging evidence have revealed significant contributions of CUB domain-containing protein-1 (CDCP1) in tumorigenesis, including colon, renal, ovarian, pancreatic, prostate and breast cancers. However, the roles of CDCP1 in cervical cancer (CC) still remain elusive. Materials and Methods: Quantitative reverse transcription polymerase chain reaction, immunohistochemistry and Western blotting were used to confirm the expression of CDCP1 in CC tissues compared with matched non-tumor tissues. In vitro, gain-of-function and loss-of-function studies were used to investigate the biological function and underlying mechanism of CDCP1 in cervical carcinogenesis. Furthermore, tumor growth was evaluated using a xenogenous subcutaneously implant model of CC cells in vivo. Results: Here, we confirmed that CDCP1 was significantly increased in human CC both in mRNA and in protein levels compared to normal cervical tissues. Furthermore, we demonstrated that increased CDCP1 expression promotes proliferation, migration, invasion and mediates the epithelial-to-mesenchymal transition phenotype in HeLa and C33A cells. Also, CDCP1 knockdown reverses all the effects of enhanced CDCP1 on cell behavior in SiHa and Caski cells. Importantly, the suppressive expression of CDCP1 repressed tumor growth in a mouse xenograft model of CC. Conclusion: In summary, our current study results provide novel insights into the role of CDCP1 in CC progression. Potentially, CDCP1 might serve as a diagnostic biomarker and a novel therapeutic target for CC.

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Section: Discussionmentioning

confidence: 77%

Section: Introductionmentioning

confidence: 99%

<p>CUB Domain-Containing Protein-1 Promotes Proliferation, Migration and Invasion in Cervical Cancer Cells</p>

Huang¹,

Chen²,

Lai³

et al. 2020

CMAR

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“…The mechanism is that the direct binding of H19 to miR-141 activates the Wnt/β-catenin signaling pathway in tumor cells ( 131 ). As mentioned earlier, the activation of the Wnt/β-catenin signaling pathway has been shown to promote the metastasis of CRC ( 82 ). Besides, H19 overexpression is also an important factor inducing CRC metastasis ( 132 ).…”

Section: The Regulation Of Cafs-related Lncrnas On the Metastasis Of mentioning

confidence: 83%

“…Wnt/β-catenin signaling pathway is one of the key pathways regulating tumor development. To date, activation of the Wnt/β-catenin signaling pathway has been proved to contribute to the metastasis of lung cancer ( 81 ), CRC ( 82 ), breast cancer ( 83 ), and OSCC ( 39 , 45 ). Studies have shown that lncRNAs are important factors in regulating the Wnt/β-catenin signaling pathway of OSCC cells.…”

Section: Overview Of Lncrnas Involved In Oscc Metastasismentioning

confidence: 99%

Long Noncoding RNAs in the Metastasis of Oral Squamous Cell Carcinoma

Jiang²,

Shao³

et al. 2021

Front. Oncol.

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Oral squamous cell carcinoma (OSCC) is a common malignant tumor worldwide. Metastasis is the main cause of the death of OSCC patients. Long noncoding RNAs (lncRNAs), one of the key factors affecting OSCC metastasis, are a subtype of RNA with a length of more than 200 nucleotides that has little or no coding potential. In recent years, the important role played by lncRNAs in biological processes, such as chromatin modification, transcription regulation, RNA stability regulation, and mRNA translation, has been gradually revealed. More and more studies have shown that lncRNAs can regulate the metastasis of various tumors including OSCC at epigenetic, transcriptional, and post-transcriptional levels. In this review, we mainly discussed the role and possible mechanisms of lncRNAs in OSCC metastasis. Most lncRNAs act as oncogenes and only a few lncRNAs have been shown to inhibit OSCC metastasis. Besides, we briefly introduced the research status of cancer-associated fibroblasts-related lncRNAs in OSCC metastasis. Finally, we discussed the research prospects of lncRNAs-mediated crosstalk between OSCC cells and the tumor microenvironment in OSCC metastasis, especially the potential research value of exosomes and lymphangiogenesis. In general, lncRNAs are expected to be used for screening, treatment, and prognosis monitoring of OSCC metastasis, but more work is still required to better understand the biological function of lncRNAs.

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“…These genes function by altering the activities of several intracellular signaling pathways, such as Notch, NF-κB, MAPK, and AKT signaling pathways (Agarwal et al, 2017;Wang et al, 2018;Xu J. et al, 2018;Jackstadt et al, 2019). Key regulators of Wnt signaling, β-catenin and E-cadherin were reported to be activated by various genes and to promote CRC metastasis (Wang et al, 2016;Dong et al, 2017;Zhang et al, 2018;He et al, 2019;Li et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

CCMAlnc Promotes the Malignance of Colorectal Cancer by Modulating the Interaction Between miR-5001-5p and Its Target mRNA

Yan

Xuan

Gao

et al. 2020

Front. Cell Dev. Biol.

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ObjectiveColorectal cancer (CRC) is highly malignant and cancer metastasis remains the predominant cause of CRC death. The potential molecular mechanism of long non-coding RNA (lncRNAs) in CRC malignance is still poorly elucidated.MethodsCCMAlnc expression was analyzed by using the Sequence ReadArchive (SRA) database. Target gene expression was examined by real-time PCR and Western blotting. The biological function of CCMAlnc and miR-5001-5p was detected by cell invasion, CCK8 proliferation, and colony formation assays in loss of function and gain of function experiments in vitro. A luciferase assay was performed to validate the target site of miR-5001-5p on the 3′-UTR of HES6 mRNA.ResultsCCMAlnc was identified as a novel functional lncRNA in CRC. Elevated CCMAlnc was detected in CRC cells as well as in clinical CRC tissue samples, and the expression of this lncRNA positively correlated with the poor prognosis of CRC patients. Functional validation assays revealed that downregulation of CCMAlnc impaired CRC cell proliferation and invasion in vitro, but upregulation of CCMAlnc reversed this effect. Moreover, CCMAlnc was validated to act as a competing endogenous RNA (ceRNA) that stabilizes the expression of HES6 by downregulating miR-5001-5p.ConclusionCCMAlnc/miR-5001-5p/HES6 signaling is strongly activated to promote CRC malignance. CCMAlnc is defined as a potential candidate biomarker for metastasis prediction in CRC patients and as a potential therapeutic target for CRC treatment.

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CDCP1 enhances Wnt signaling in colorectal cancer promoting nuclear localization of β-catenin and E-cadherin

Cited by 33 publications

References 47 publications

<p>CUB Domain-Containing Protein-1 Promotes Proliferation, Migration and Invasion in Cervical Cancer Cells</p>

<p>CUB Domain-Containing Protein-1 Promotes Proliferation, Migration and Invasion in Cervical Cancer Cells</p>

Long Noncoding RNAs in the Metastasis of Oral Squamous Cell Carcinoma

CCMAlnc Promotes the Malignance of Colorectal Cancer by Modulating the Interaction Between miR-5001-5p and Its Target mRNA

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