RANK Ligand Modulation of Autophagy in Oral Squamous Cell Carcinoma Tumor Cells

Yuvaraj Sambandam, Sashank Sakamuri, Sundaravadivel Balasubramanian, Azizul Haque*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Autophagy is a cellular process to recycle nutrients and has been implicated in cancer treatment. Oral squamous cell carcinoma (OSCC) is the most common oral cancer which ranks 3% of cancers in men and 2% in women. In this study, immunohistochemical staining of OSCC tumor specimens from human subjects and an athymic mouse model demonstrated high levels of autophagy markers LC3-II and ATG5 expression. Further, we identified high levels LC3-II expression in OSCC tumor cell lines (SCC-1, SCC-12, and SCC-14a) compared to normal human epithelial (RWPE-1) cells. OSCC cells express high levels of RANK ligand (RANKL); however, a functional role in autophagy is unknown. Interestingly, RANKL stimulation significantly increased autophagosome-related gene expressions such as LC3, ATG5, BECN1, and PI3KC3 mRNA expression in OSCC cells. Further, Western blot analysis of total cell lysates demonstrated a dose-dependent increase in LC3-II and ATG5 expression in RANKL-stimulated cells. In addition, RANKL increased expression of LC3-I and LC3-II, essential for autophagosome formation. Confocal microscopy analysis of LC3-II and localization with lysosome further confirms autophagosome formation in response to RANKL treatment in OSCC cells. Collectively, our results indicate a novel function of RANKL to induce autophagosome formation, and could be a potential therapeutic target to control OSCC tumor progression. J. Cell. Biochem. 117: 118-125, 2016.

Original languageEnglish (US)
Pages (from-to)118-125
Number of pages8
JournalJournal of Cellular Biochemistry
Issue number1
StatePublished - Jan 1 2016


  • ATG5
  • LC3

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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