title: 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: Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.|University of the Chinese Academy of Sciences, Shanghai 200031, China.
authors: Lele
authors: L
authors: Song
authors: Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.|University of the Chinese Academy of Sciences, Shanghai 200031, China.
authors: Renxu
authors: R
authors: Chang
authors: Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.|University of the Chinese Academy of Sciences, Shanghai 200031, China.
authors: Cheng
authors: C
authors: Dai
authors: Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.|University of the Chinese Academy of Sciences, Shanghai 200031, China.
authors: Yanjun
authors: Y
authors: Wu
authors: Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.|University of the Chinese Academy of Sciences, Shanghai 200031, China.
authors: Jingyu
authors: J
authors: Guo
authors: Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors: Meiyan
authors: M
authors: Qi
authors: Department of Medicine, College of Medicine and Health, Lishui University, Lishui 323000, China.
authors: Wu
authors: W
authors: Zhou
authors: Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors: Lixing
authors: L
authors: Zhan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D061986:MCF-7 Cells; D008297:Male; D008819:Mice, Nude; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D011554:Pseudopodia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D008840:Microfilament Proteins; D016755:Proto-Oncogene Proteins c-jun; C432967:SORBS1 protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D048031:JNK Mitogen-Activated Protein Kinases
keywords: JNK; SORBS1; cisplatin sensitivity; invasion; migration