Please use this identifier to cite or link to this item: https://doi.org/10.7150/thno.47001
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dc.titleLAMA4 upregulation is associated with high liver metastasis potential and poor survival outcome of Pancreatic Cancer
dc.contributor.authorZheng, B.
dc.contributor.authorQu, J.
dc.contributor.authorOhuchida, K.
dc.contributor.authorFeng, H.
dc.contributor.authorChong, Stephen Jun Fei
dc.contributor.authorYan, Z.
dc.contributor.authorPiao, Y.
dc.contributor.authorLiu, P.
dc.contributor.authorSheng, N.
dc.contributor.authorEguchi, D.
dc.contributor.authorOhtsuka, T.
dc.contributor.authorMizumoto, K.
dc.contributor.authorLiu, Z.
dc.contributor.authorPervaiz, S.
dc.contributor.authorGong, P.
dc.contributor.authorNakamura, M.
dc.date.accessioned2021-08-25T09:13:02Z
dc.date.available2021-08-25T09:13:02Z
dc.date.issued2020
dc.identifier.citationZheng, B., Qu, J., Ohuchida, K., Feng, H., Chong, Stephen Jun Fei, Yan, Z., Piao, Y., Liu, P., Sheng, N., Eguchi, D., Ohtsuka, T., Mizumoto, K., Liu, Z., Pervaiz, S., Gong, P., Nakamura, M. (2020). LAMA4 upregulation is associated with high liver metastasis potential and poor survival outcome of Pancreatic Cancer. Theranostics 10 (22) : 10274-10289. ScholarBank@NUS Repository. https://doi.org/10.7150/thno.47001
dc.identifier.issn1838-7640
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/199231
dc.description.abstractRationale: Pancreatic cancer is one of the most difficult cancers to manage and its poor prognosis stems from the lack of a reliable early disease biomarker coupled with its highly metastatic potential. Liver metastasis accounts for the high mortality rate in pancreatic cancer. Therefore, a better understanding of the mechanism(s) underlying the acquisition of the metastatic potential in pancreatic cancer is highly desirable. Methods: Microarray analysis in wild-type and highly liver metastatic human pancreatic cancer cell lines was performed to identify gene expression signatures that underlie the metastatic process. We validated our findings in patient samples, nude mice, cell lines and database analysis. Results: We identified a metastasis-related gene, laminin subunit alpha 4 (LAMA4), that was upregulated in highly liver metastatic human pancreatic cancer cell lines. Downregulation of LAMA4 reduced the liver metastatic ability of pancreatic cancer cells in vivo. Furthermore, LAMA4 expression was positively correlated with tumor severity and in silico analyses revealed that LAMA4 was associated with altered tumor microenvironment. In particular, our in vitro and in vivo results showed that LAMA4 expression was highly correlated with cancer-associated fibroblasts (CAFs) level which may contribute to pancreatic cancer metastasis. We further found that LAMA4 had a positive effect on the recruitment and activity of CAFs. Conclusions: These data provide evidence for LAMA4 as a possible biomarker of disease progression and poor prognosis in pancreatic cancer. Our findings indicate that LAMA4 may contribute to pancreatic cancer metastasis via recruitment or activation of CAFs. © 2020 Ivyspring International Publisher. All rights reserved.
dc.publisherIvyspring International Publisher
dc.rightsAttribution-NonCommercial 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/
dc.sourceScopus OA2020
dc.subjectCancer-associated fibroblasts
dc.subjectLAMA4
dc.subjectMetastasis
dc.subjectPancreatic cancer
dc.subjectTumor severity
dc.typeArticle
dc.contributor.departmentDEPT OF PHYSIOLOGY
dc.description.doi10.7150/thno.47001
dc.description.sourcetitleTheranostics
dc.description.volume10
dc.description.issue22
dc.description.page10274-10289
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