CD133 confers cancer stem-like cell properties by stabilizing EGFR-AKT signaling in hepatocellular carcinoma

Jae Woo Jang, Yeonhwa Song, Se Hyuk Kim, Jin sun Kim, Kang mo Kim, Eun Kyung Choi, Joon Kim, Haeng Ran Seo

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Hepatocellular carcinoma (HCC) is the seventh most common malignant tumor and the third leading cause of cancer-related death in the world. Cancer stem cells (CSCs) are small subpopulation of cells within tumors that drive chemoresistance and tumor recurrence in various cancers. We characterized CSCs in primary HCC and identified CD133 as a CSC surface marker. CD133+ HCC cells displayed more stem cell-like properties, tumor spheroid-forming ability, chemoresistance, migration ability, and tumorigenic capacity than CD133- HCC cells. The biological function and molecular mechanism of CD133 remain unclear. HCC cell lines with a high level of CD133 expression overexpressed EGFR, which is overexpressed in approximately 70% of conventional HCCs. CD133 depletion destabilized EGFR by augmenting EGFR internalization and thus inhibited EGFR-AKT signaling. CD133 would therefore serve to sustain aberrant EGFR-mediated oncogenic signaling. Furthermore, EGFR-deficient CD133+ HCC cells manifested greater sensitivity to anticancer drugs and less spheroid-formation capacity than control CD133+ HCC cells. Our results strongly indicate that CD133 facilitates CSC-like properties by stabilizing EGFR-AKT signaling in HCC. It might therefore be feasible to use CD133 as a novel target to sensitize HCC cells that manifest resistance to EGFR-targeted therapy.

Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalCancer Letters
Volume389
DOIs
Publication statusPublished - 2017 Mar 28

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Neoplastic Stem Cells
Stem cells
Hepatocellular Carcinoma
Tumors
Cells
Neoplasms
Pharmaceutical Preparations
Stem Cells
Recurrence
Cell Line

Keywords

  • Cancer stem cells (CSCs)
  • CD133
  • Epidermal growth factor receptor (EGFR)
  • Hepatocellular carcinoma (HCC)

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

CD133 confers cancer stem-like cell properties by stabilizing EGFR-AKT signaling in hepatocellular carcinoma. / Jang, Jae Woo; Song, Yeonhwa; Kim, Se Hyuk; Kim, Jin sun; Kim, Kang mo; Choi, Eun Kyung; Kim, Joon; Seo, Haeng Ran.

In: Cancer Letters, Vol. 389, 28.03.2017, p. 1-10.

Research output: Contribution to journalArticle

Jang, Jae Woo ; Song, Yeonhwa ; Kim, Se Hyuk ; Kim, Jin sun ; Kim, Kang mo ; Choi, Eun Kyung ; Kim, Joon ; Seo, Haeng Ran. / CD133 confers cancer stem-like cell properties by stabilizing EGFR-AKT signaling in hepatocellular carcinoma. In: Cancer Letters. 2017 ; Vol. 389. pp. 1-10.
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