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Updated: Sep 25, 2025

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
Published on: July 21, 2018
SHANK1 facilitates non-small cell lung cancer processes through modulating the ubiquitination of Klotho by
Bo Chen1, Hongye Zhao1, Min Li1
1Department of Geriatrics, Jiangsu Provincial Key Laboratory of Geriatrics, First Affiliated Hospital, Nanjing Medical University, 210029, Nanjing, China.
Abstract:
SH3 and multiple ankyrin repeat domains 1 (SHANK1) is a scaffold protein, plays an important role in the normal function of neuron system. It has recently been shown to be a potential oncogene. In the present study, we report that the expression of SHANK1 is upregulated in non-small cell lung cancer (NSCLC), and is correlated with clinic pathological characteristics of NSCLC. Moreover, SHANK1 overexpression enhances the proliferation, migration and invasion of NSCLC cells. Mouse cell-derived xenograft model also confirmed the effects of SHANK1 on tumor growth in vivo. Furthermore, we found that SHANK1 increases the protein degradation of Klotho (KL), an important tumor suppressor, through ubiquitination-dependent pathway. In particular, we report discovery of KL as a SHANK1-interacting protein that acts as a new substate of the E3 ubiquitin ligase MDM2. SHANK1 can form a complex with KL and MDM2 and enhance the interaction between KL and MDM2. Our findings reveal an important oncogenic role and mechanism of SHANK1, suggesting SHANK1 can be a potential therapeutic target in NSCLC.
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