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.
Keywords: JNK; SORBS1; cisplatin sensitivity; invasion; migration.