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
Volume Number7
Issue Number16
Pages21644 - 21657
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