Stress-induced phosphoprotein-1 maintains the stability of JAK2 in cancer cells

Chia Lung Tsai, Angel Chao, Shih Ming Jung, Chi Neu Tsai, Chiao Yun Lin, Shun Hua Chen, Shih Che Sue, Tzu Hao Wang*, Hsin Shih Wang, Chyong Huey Lai

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

27 Scopus citations


Overexpression of stress-induced phosphoprotein 1 (STIP1) - a co-chaperone of heat shock protein (HSP) 70/HSP90 - and activation of the JAK2-STAT3 pathway occur in several tumors. Combined treatment with a HSP90 inhibitor and a JAK2 inhibitor exert synergistic anti-cancer effects. Here, we show that STIP1 stabilizes JAK2 protein in ovarian and endometrial cancer cells. Knock-down of endogenous STIP1 decreased JAK2 and phospho-STAT3 protein levels. The N-terminal fragment of STIP1 interacts with the N-terminus of JAK2, whereas the C-terminal DP2 domain of STIP1 mediates the interaction with HSP90 and STAT3. A peptide fragment in the DP2 domain of STIP1 (peptide 520) disrupted the interaction between STIP1 and HSP90 and induced cell death through JAK2 suppression. In an animal model, treatment with peptide 520 inhibited tumor growth. In summary, STIP1 modulates the function of the HSP90-JAK2-STAT3 complex. Peptide 520 may have therapeutic potential in the treatment of JAK2-overexpressing tumors.

Original languageEnglish
Pages (from-to)50548-50563
Number of pages16
Issue number31
StatePublished - 2016


  • Cancer
  • JAK2
  • STIP1


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