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Polymeric immunoglobulin receptor promotes tumor growth in hepatocellular carcinoma.

著者 Yue X , Ai J , Xu Y , Chen Y , Huang M , Yang X , Hu B , Zhang H , He C , Yang X , Tang W , Peng X , Dong L , Wang H , Fan J , Ding J , Geng M
Hepatology.2017 Jan 10 ; ():.
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Deregulation of the immune system is believed to contribute to cancer malignancy, which has led to recent therapeutic breakthroughs facilitating antitumor immunity. In a malignant setting, immunoglobulin receptors, which are fundamental components of the human immune system, fulfill paradoxical roles in cancer pathogenesis. This study describes a previously unrecognized pro-oncogenic function of polymeric immunoglobulin receptor (pIgR) in the promotion of cell transformation and proliferation. Mechanistically, pIgR overexpression is associated with Yes activation, which is required for pIgR-induced oncogenic growth. Specifically, pIgR activates the Yes-Dap12-Syk-Rac1/CDC42-MEK/ERK cascade in an immunoreceptor tyrosine-based activating motif (ITAM)-dependent manner to promote cell transformation and tumor growth, although pIgR itself does not contain an ITAM sequence. Additionally, the combination of pIgR and phosphorylated Yes (p-Yes) levels serves as a prognostic biomarker for hepatitis B surface antigen (HBsAg)-positive and early stage hepatocellular carcinoma (HCC) patients. Moreover, pharmacological targeting of MEK/ERK or Yes represents a therapeutic option for the subgroup of patients with pIgR/p-Yes-positive HCC based on our results with both cancer cell line-based xenografts and primary patient-derived xenografts.
PMID: 28073159 [PubMed - as supplied by publisher]
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