SORBS1 suppresses tumor metastasis and improves the sensitivity of cancer to chemotherapy drug.

Abstract	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.
Authors	Lele Song, Renxu Chang, Cheng Dai, Yanjun Wu, Jingyu Guo, Meiyan Qi, Wu Zhou, Lixing Zhan
Journal	Oncotarget (Oncotarget) Vol. 8 Issue 6 Pg. 9108-9122 (Feb 07 2017) ISSN: 1949-2553 [Electronic] United States
PMID	27791200 (Publication Type: Journal Article)
Chemical References	Antineoplastic Agents Microfilament Proteins Proto-Oncogene Proteins c-jun SORBS1 protein, human TP53 protein, human Tumor Suppressor Protein p53 JNK Mitogen-Activated Protein Kinases
Topics	Animals Antineoplastic Agents (pharmacology) Breast Neoplasms (drug therapy, genetics, metabolism, pathology) Cell Movement (drug effects) Epithelial-Mesenchymal Transition (drug effects) Female Gene Expression Regulation, Neoplastic Humans JNK Mitogen-Activated Protein Kinases (metabolism) Kaplan-Meier Estimate MCF-7 Cells Male Mice, Nude Microfilament Proteins (genetics, metabolism) Neoplasm Invasiveness Neoplasm Metastasis Proto-Oncogene Proteins c-jun (metabolism) Pseudopodia (drug effects, metabolism, pathology) RNA Interference Signal Transduction (drug effects) Time Factors Transfection Tumor Suppressor Protein p53 (genetics, metabolism) Xenograft Model Antitumor Assays

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