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Fig. 6 | Cancer Cell International

Fig. 6

From: DAB2IP predicts treatment response and prognosis of ESCC patients and modulates its radiosensitivity through enhancing IR-induced activation of the ASK1-JNK pathway

Fig. 6

Proposed schematic representation for the molecular mechanism of DAB2IP-inducedregulation of radiosensitivity in ESCC cells. In ESCC cells with low or no expression of DAB2IP, IR causes increased levels of intracellular reactive oxygen species (ROS), leading to the dephosphorylation of Ser-966 of ASK1, which consequently triggers dissociation of Trx and 14-3-3 from ASK1, ultimately resulting in a basic activated status of the ASK1-JNK pathway and causing ESCC cells to exhibit low sensitivity/or resistance to radiotherapy. In ESCC cells with normal or overexpression of DAB2IP, the IR-induced ROS stimulates dephosphorylation of Ser-966 of ASK1, thereby releasing of 14-3-3 and Trx from ASK1. This step is necessary but not sufficient for ASK1-enhanced activation. After 14-3-3 and Trx are released from ASK1, DAB2IP preferentially binds to the locus surrounding the Ser966-dephosphorylated site of ASK1, which consequently facilitates dissociation of 14-3-3 from ASK1 and enhances ASK1 kinase activity, ultimately leading to an over-activation of ASK1-JNK signaling and ESCC cells with high sensitivity to radiotherapy

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Cancer Cell International

ISSN: 1475-2867

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