Research Papers:

Shp2 confers cisplatin resistance in small cell lung cancer via an AKT-mediated increase in CA916798

Xuemei Yang, Chunlan Tang, Hu Luo, Haijing Wang and Xiangdong Zhou _

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Oncotarget. 2017; 8:23664-23674. https://doi.org/10.18632/oncotarget.15641

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Xuemei Yang1,2, Chunlan Tang1, Hu Luo1, Haijing Wang1, Xiangdong Zhou1

1Department of Respiratory, Southwest Hospital, Third Military Medical University, Shapingba District, Chongqing 400038, PR China

2Department of Respiratory, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Yuzhong District, Chongqing 400042, PR China

Correspondence to:

Xiangdong Zhou, email: [email protected]

Keywords: small cell lung cancer, cisplatin resistance, SHP2, AKT, CA916798

Received: April 08, 2016     Accepted: December 05, 2016     Published: February 23, 2017


The tyrosine phosphatase Shp2 is associated with tumorigenesis in small cell lung cancer (SCLC). However, the relationship between Shp2 and resistance to chemotherapy remains unclear. Here, we show that Shp2 plays an important role in inducing resistance to cisplatin-based chemotherapy via the SHP2-AKT-CA916798 pathway. In an SCLC cell line, overexpression of Shp2 induced cisplatin resistance and the increased expression of AKT, pAKT, pmTOR, and CA916798. Conversely, depletion of Shp2 in a cisplatin-resistant cell line via RNA interference increased cisplatin sensitivity and decreased AKT, pAKT, pmTOR, and CA916798 expression levels. Activation of AKT stimulated CA916798 expression and altered the level of Shp2. A mouse xenograft model verified the results obtained from the in vitro experiments. In addition, we collected and analyzed clinical SCLC specimens and found that Shp2 levels correlated with CA916798 expression in tumor tissues. Importantly, higher levels of Shp2 or CA916798 were associated with a poorer prognosis in SCLC patients who received chemotherapy. Together, our findings indicate that Shp2 induces cisplatin resistance in SCLC patients via the SHP2-AKT-CA916798 pathway. Therefore, Shp2 and CA916798 may be promising biomarkers for predicting resistance to chemotherapy and may function as targets for enhancing treatments.

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