Autocrine TNFα Signaling Renders Human Cancer Cells Susceptible to Smac-Mimetic-Induced Apoptosis

Sean L. Petersen, Lai Wang, Asligul Yalcin-Chin, Lin Li, Michael Peyton, John Minna, Patrick Harran, Xiaodong Wang

Research output: Contribution to journalArticle

410 Citations (Scopus)

Abstract

A small-molecule mimetic of Smac/Diablo that specifically counters the apoptosis-inhibiting activity of IAP proteins has been shown to enhance apoptosis induced by cell surface death receptors as well as chemotherapeutic drugs. Survey of a panel of 50 human non-small-cell lung cancer cell lines has revealed, surprisingly, that roughly one-quarter of these lines are sensitive to the treatment of Smac mimetic alone, suggesting that an apoptotic signal has been turned on in these cells and is held in check by IAP proteins. This signal has now been identified as the autocrine-secreted cytokine tumor necrosis factor alpha (TNFα). In response to autocrine TNFα signaling, the Smac mimetic promotes formation of a RIPK1-dependent caspase-8-activating complex, leading to apoptosis.

Original languageEnglish (US)
Pages (from-to)445-456
Number of pages12
JournalCancer Cell
Volume12
Issue number5
DOIs
StatePublished - Nov 13 2007

Fingerprint

Tumor Necrosis Factor-alpha
Apoptosis
Neoplasms
Death Domain Receptors
Caspase 8
Cell Surface Receptors
Non-Small Cell Lung Carcinoma
Proteins
Cell Death
Cytokines
Cell Line
Pharmaceutical Preparations
Surveys and Questionnaires
aposome

Keywords

  • CELLCYCLE

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

Cite this

Autocrine TNFα Signaling Renders Human Cancer Cells Susceptible to Smac-Mimetic-Induced Apoptosis. / Petersen, Sean L.; Wang, Lai; Yalcin-Chin, Asligul; Li, Lin; Peyton, Michael; Minna, John; Harran, Patrick; Wang, Xiaodong.

In: Cancer Cell, Vol. 12, No. 5, 13.11.2007, p. 445-456.

Research output: Contribution to journalArticle

Petersen, SL, Wang, L, Yalcin-Chin, A, Li, L, Peyton, M, Minna, J, Harran, P & Wang, X 2007, 'Autocrine TNFα Signaling Renders Human Cancer Cells Susceptible to Smac-Mimetic-Induced Apoptosis', Cancer Cell, vol. 12, no. 5, pp. 445-456. https://doi.org/10.1016/j.ccr.2007.08.029
Petersen, Sean L. ; Wang, Lai ; Yalcin-Chin, Asligul ; Li, Lin ; Peyton, Michael ; Minna, John ; Harran, Patrick ; Wang, Xiaodong. / Autocrine TNFα Signaling Renders Human Cancer Cells Susceptible to Smac-Mimetic-Induced Apoptosis. In: Cancer Cell. 2007 ; Vol. 12, No. 5. pp. 445-456.
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