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CD133 Stimulates Cell Proliferation via the Upregulation of Amphiregulin in Melanoma.
Simbulan-Rosenthal, Cynthia M; Islam, Nusrat; Haribabu, Yogameenakshi; Alobaidi, Ryyan; Shalamzari, Azadeh; Graham, Garrett; Kuo, Li-Wei; Sykora, Peter; Rosenthal, Dean S.
Affiliation
  • Simbulan-Rosenthal CM; Department of Biochemistry and Molecular & Cellular Biology, Georgetown University School of Medicine, Washington, DC 20057, USA.
  • Islam N; Department of Biochemistry and Molecular & Cellular Biology, Georgetown University School of Medicine, Washington, DC 20057, USA.
  • Haribabu Y; Department of Biochemistry and Molecular & Cellular Biology, Georgetown University School of Medicine, Washington, DC 20057, USA.
  • Alobaidi R; Department of Biochemistry and Molecular & Cellular Biology, Georgetown University School of Medicine, Washington, DC 20057, USA.
  • Shalamzari A; Department of Biochemistry and Molecular & Cellular Biology, Georgetown University School of Medicine, Washington, DC 20057, USA.
  • Graham G; Department of Biochemistry and Molecular & Cellular Biology, Georgetown University School of Medicine, Washington, DC 20057, USA.
  • Kuo LW; Department of Biochemistry and Molecular & Cellular Biology, Georgetown University School of Medicine, Washington, DC 20057, USA.
  • Sykora P; Amelia Technologies, LLC., Washington, DC 20001, USA.
  • Rosenthal DS; Department of Biochemistry and Molecular & Cellular Biology, Georgetown University School of Medicine, Washington, DC 20057, USA.
Cells ; 13(9)2024 May 02.
Article in En | MEDLINE | ID: mdl-38727313
ABSTRACT
CD133, a cancer stem cell (CSC) marker in tumors, including melanoma, is associated with tumor recurrence, chemoresistance, and metastasis. Patient-derived melanoma cell lines were transduced with a Tet-on vector expressing CD133, generating doxycycline (Dox)-inducible cell lines. Cells were exposed to Dox for 24 h to induce CD133 expression, followed by RNA-seq and bioinformatic analyses, revealing genes and pathways that are significantly up- or downregulated by CD133. The most significantly upregulated gene after CD133 was amphiregulin (AREG), validated by qRT-PCR and immunoblot analyses. Induced CD133 expression significantly increased cell growth, percentage of cells in S-phase, BrdU incorporation into nascent DNA, and PCNA levels, indicating that CD133 stimulates cell proliferation. CD133 induction also activated EGFR and the MAPK pathway. Potential mechanisms highlighting the role(s) of CD133 and AREG in melanoma CSC were further delineated using AREG/EGFR inhibitors or siRNA knockdown of AREG mRNA. Treatment with the EGFR inhibitor gefitinib blocked CD133-induced cell growth increase and MAPK pathway activation. Importantly, siRNA knockdown of AREG reversed the stimulatory effects of CD133 on cell growth, indicating that AREG mediates the effects of CD133 on cell proliferation, thus serving as an attractive target for novel combinatorial therapeutics in melanoma and cancers with overexpression of both CD133 and AREG.
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Full text: 1 Database: MEDLINE Main subject: Cell Proliferation / Amphiregulin / AC133 Antigen / Melanoma Limits: Humans Language: En Year: 2024 Type: Article

Full text: 1 Database: MEDLINE Main subject: Cell Proliferation / Amphiregulin / AC133 Antigen / Melanoma Limits: Humans Language: En Year: 2024 Type: Article