A COL11A1-correlated pan-cancer gene signature of activated fibroblasts for the prioritization of therapeutic targets

Dongyu Jia, Zhenqiu Liu, Nan Deng, Tuan Zea Tan, Ruby Yun Ju Huang, Barbie Taylor-Harding, Dong Joo Cheon, Kate Lawrenson, Wolf R. Wiedemeyer, Ann E. Walts, Beth Y. Karlan, Sandra Orsulic

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Although cancer-associated fibroblasts (CAFs) are viewed as a promising therapeutic target, the design of rational therapy has been hampered by two key obstacles. First, attempts to ablate CAFs have resulted in significant toxicity because currently used biomarkers cannot effectively distinguish activated CAFs from non-cancer associated fibroblasts and mesenchymal progenitor cells. Second, it is unclear whether CAFs in different organs have different molecular and functional properties that necessitate organ-specific therapeutic designs. Our analyses uncovered COL11A1 as a highly specific biomarker of activated CAFs. Using COL11A1 as a ‘seed’, we identified co-expressed genes in 13 types of primary carcinoma in The Cancer Genome Atlas. We demonstrated that a molecular signature of activated CAFs is conserved in epithelial cancers regardless of organ site and transforming events within cancer cells, suggesting that targeting fibroblast activation should be effective in multiple cancers. We prioritized several potential pan-cancer therapeutic targets that are likely to have high specificity for activated CAFs and minimal toxicity in normal tissues.

Original languageEnglish (US)
Pages (from-to)203-214
Number of pages12
JournalCancer Letters
Volume382
Issue number2
DOIs
StatePublished - Nov 28 2016

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'A COL11A1-correlated pan-cancer gene signature of activated fibroblasts for the prioritization of therapeutic targets'. Together they form a unique fingerprint.

  • Cite this

    Jia, D., Liu, Z., Deng, N., Tan, T. Z., Huang, R. Y. J., Taylor-Harding, B., Cheon, D. J., Lawrenson, K., Wiedemeyer, W. R., Walts, A. E., Karlan, B. Y., & Orsulic, S. (2016). A COL11A1-correlated pan-cancer gene signature of activated fibroblasts for the prioritization of therapeutic targets. Cancer Letters, 382(2), 203-214. https://doi.org/10.1016/j.canlet.2016.09.001