SORBS1 suppresses tumor metastasis and improves the sensitivity of cancer to chemotherapy drug
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Lele Song1,2, Renxu Chang1,2, Cheng Dai1,2, Yanjun Wu1,2, Jingyu Guo1,2, Meiyan Qi1, Wu Zhou3, Lixing Zhan1
1Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
2University of the Chinese Academy of Sciences, Shanghai 200031, China
3Department of Medicine, College of Medicine and Health, Lishui University, Lishui 323000, China
Lixing Zhan, email: [email protected]
Wu Zhou, email: [email protected]
Keywords: SORBS1, migration, invasion, JNK, cisplatin sensitivity
Received: January 10, 2016 Accepted: October 12, 2016 Published: October 24, 2016
Tumor metastasis and invasion are both hallmarks of cancer malignancy and the leading cause of cancer death. Here we show that the adaptor protein SORBS1 (Sorbin and SH3 domain-containing protein 1, also known as CAP/ponsin) is expressed at low levels in clinical cancer samples. In addition, low-level expression of SORBS1 was significantly associated with poor clinical outcomes and the increased tumor cell invasive capacity in breast cancer patients. We demonstrate that depletion of SORBS1 increases protrusions and filopodium-like protrusions (FLPs) formation, as well as the migratory and invasive abilities of cancer cells, via activation of JNK/cJun. Furthermore, silencing of SORBS1 promotes the epithelial-to-mesenchymal transition (EMT) process and attenuates chemical drug sensitivity especially that to cisplatin, by inhibition of p53 in breast cancer cells. Thus, we illustrate that SORBS1 is a potential inhibitor of metastasis in cancer and may be a promising target in chemotherapy.
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