Key roles of necroptotic factors in promoting tumor growth.

Published

Journal Article

Necroptotic factors are generally assumed to play a positive role in tumor therapy by eliminating damaged tumor cells. Here we show that, contrary to expectation, necroptotic factors RIPK1, RIPK3, and MLKL promote tumor growth. We demonstrate that genetic knockout of necroptotic genes RIPK1, RIPK3, or MLKL in cancer cells significantly attenuated their abilities to grow in an anchorage-independent manner. In addition, they exhibited significantly enhanced radiosensitivity. The knockout cells also showed greatly reduced ability to form tumors in mice. Moreover, necrosulfonamide (NSA), a previously identified chemical inhibitor of necroptosis, could significantly delay tumor growth in a xenograft model. Mechanistically, we show that necroptoic factors play a significant role in maintaining the activity of NF-κB. Finally, we found that high levels of phosphorylated MLKL in human esophageal and colon cancers are associated with poor overall survival. Taken together, we conclude that pro-necroptic factors such as RIPK1, RIPK3, and MLKL may play a role in supporting tumor growth, and MLKL may be a promising target for cancer treatment.

Full Text

Duke Authors

Cited Authors

  • Liu, X; Zhou, M; Mei, L; Ruan, J; Hu, Q; Peng, J; Su, H; Liao, H; Liu, S; Liu, W; Wang, H; Huang, Q; Li, F; Li, C-Y

Published Date

  • April 19, 2016

Published In

Volume / Issue

  • 7 / 16

Start / End Page

  • 22219 - 22233

PubMed ID

  • 26959742

Pubmed Central ID

  • 26959742

Electronic International Standard Serial Number (EISSN)

  • 1949-2553

Digital Object Identifier (DOI)

  • 10.18632/oncotarget.7924

Language

  • eng

Conference Location

  • United States