Exp Mol Med.  2014 Dec;46(12):e124. 10.1038/emm.2014.74.

Inhibition of phospholipase D2 induces autophagy in colorectal cancer cells

• Hwang WC
• Kim MK
• Song JH
• Choi KY
• Min DS

• KMID: 2155389
• DOI: http://doi.org/10.1038/emm.2014.74

Abstract

Autophagy is a conserved lysosomal self-digestion process used for the breakdown of long-lived proteins and damaged organelles, and it is associated with a number of pathological processes, including cancer. Phospholipase D (PLD) isozymes are dysregulated in various cancers. Recently, we reported that PLD1 is a new regulator of autophagy and is a potential target for cancer therapy. Here, we investigated whether PLD2 is involved in the regulation of autophagy. A PLD2-specific inhibitor and siRNA directed against PLD2 were used to treat HT29 and HCT116 colorectal cancer cells, and both inhibition and genetic knockdown of PLD2 in these cells significantly induced autophagy, as demonstrated by the visualization of light chain 3 (LC3) puncta and autophagic vacuoles as well as by determining the LC3-II protein level. Furthermore, PLD2 inhibition promoted autophagic flux via the canonical Atg5-, Atg7- and AMPK-Ulk1-mediated pathways. Taken together, these results suggest that PLD2 might have a role in autophagy and that its inhibition might provide a new therapeutic basis for targeting autophagy.

MeSH Terms

Autophagy/*drug effects
Cell Line, Tumor
Colorectal Neoplasms/enzymology/*genetics/*therapy
Genetic Therapy
HCT116 Cells
Humans
Phospholipase D/*antagonists & inhibitors/*genetics/metabolism
Quinolines/*pharmacology
*RNA Interference
RNA, Small Interfering/genetics/pharmacology
Signal Transduction/drug effects
Spiro Compounds/*pharmacology
Phospholipase D
Quinolines
RNA, Small Interfering
Spiro Compounds