Hepatic cancer stem cell marker granulin-epithelin precursor and beta-catenin expression associate with recurrence in hepatocellular carcinoma
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AbstractGranulin-epithelin precursor (GEP) has been demonstrated to confer enhanced cancer stem-like cell properties in hepatocellular carcinoma (HCC) cell line models in our previous studies. Here, we aimed to examine the GEP-expressing cells in relation to the stem cell related molecules and stem-like cell properties in the prospective HCC clinical cohort. GEP protein levels were significantly higher in HCCs than the paralleled non-tumor liver tissues, and associated with venous infiltration. GEP(high) cells isolated from clinical HCC samples exhibited higher levels of stem cell marker CD133, pluripotency-associated signaling molecules beta-catenin, Oct4, SOX2, Nanog, and chemodrug transporter ABCB5. In addition, GEP(high) cells possessed preferential ability to form colonies and spheroids, and enhanced in vivo tumor-initiating ability while their xenografts were able to be serially subpassaged into secondary mouse recipients. Expression levels of GEP and pluripotency-associated genes were further examined in the retrospective HCC cohort and demonstrated significant correlation of GEP with beta-catenin. Notably, HCC patients with high GEP and beta-catenin levels demonstrated poor recurrence-free survival. In summary, GEP-positive HCC cells directly isolated from clinical specimens showed beta-catenin elevation and cancer stem-like cell properties.
All Author(s) ListCheung PFY, Cheung TT, Yip CW, Ng LWC, Fung SW, Lo CM, Fan ST, Cheung ST
Journal nameOncotarget
Year2016
Month4
Day19
Volume Number7
Issue Number16
PublisherIMPACT JOURNALS LLC
Pages21644 - 21657
ISSN1949-2553
LanguagesEnglish-United Kingdom
Keywordsbeta-catenin; cancer stem cells; granulin-epithelin precursor; hepatocellular carcinoma
Web of Science Subject CategoriesCell Biology; Oncology

Last updated on 2020-16-10 at 02:14