CSRP2 suppresses colorectal cancer progression via p130Cas/Rac1 axis-meditated ERK, PAK, and HIPPO signaling pathways
| Autor: | Xunhua Liu, Shiyu Duan, Wenqing Huang, Xiaoli Long, Jun Zhou, Xuming Liu, Jianxiong Chen, Jian Geng, Jiawen Lan, Lixia Chen |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
rac1 GTP-Binding Protein 0301 basic medicine MAPK/ERK pathway Carcinogenesis Muscle Proteins Medicine (miscellaneous) Kaplan-Meier Estimate medicine.disease_cause Metastasis Mice 0302 clinical medicine Hippo Cell Movement Phosphorylation Extracellular Signal-Regulated MAP Kinases Pharmacology Toxicology and Pharmaceutics (miscellaneous) Nuclear Proteins LIM Domain Proteins Middle Aged Prognosis Gene Expression Regulation Neoplastic ERK Hippo signaling Gene Knockdown Techniques 030220 oncology & carcinogenesis Aminoquinolines Disease Progression Female Signal transduction Colorectal Neoplasms Cortactin Research Paper Signal Transduction Epithelial-Mesenchymal Transition Colon Down-Regulation RAC1 Protein Serine-Threonine Kinases Biology 03 medical and health sciences Cell Line Tumor Biomarkers Tumor medicine Animals Humans Hippo Signaling Pathway Neoplasm Invasiveness CSRP2 Cell Proliferation Hippo signaling pathway Rectum medicine.disease Colorectal cancer Xenograft Model Antitumor Assays digestive system diseases Crk-Associated Substrate Protein Pyrimidines 030104 developmental biology p21-Activated Kinases PAK Cancer research biology.protein |
| Zdroj: | Theranostics |
| ISSN: | 1838-7640 |
| DOI: | 10.7150/thno.45674 |
| Popis: | Metastasis is a major cause of death in patients with colorectal cancer (CRC). Cysteine-rich protein 2 (CSRP2) has been recently implicated in the progression and metastasis of a variety of cancers. However, the biological functions and underlying mechanisms of CSRP2 in the regulation of CRC progression are largely unknown. Methods: Immunohistochemistry, quantitative real-time polymerase chain reaction (qPCR) and Western blotting (WB) were used to detect the expression of CSRP2 in CRC tissues and paracancerous tissues. CSRP2 function in CRC was determined by a series of functional tests in vivo and in vitro. WB and immunofluorescence were used to determine the relation between CSRP2 and epithelial-mesenchymal transition (EMT). Co-immunoprecipitation and scanning electron microscopy were used to study the molecular mechanism of CSRP2 in CRC. Results: The CSRP2 expression level in CRC tissues was lower than in adjacent normal tissues and indicated poor prognosis in CRC patients. Functionally, CSRP2 could suppress the proliferation, migration, and invasion of CRC cells in vitro and inhibit CRC tumorigenesis and metastasis in vivo. Mechanistic investigations revealed a physical interaction between CSRP2 and p130Cas. CSRP2 could inhibit the activation of Rac1 by preventing the phosphorylation of p130Cas, thus activating the Hippo signaling pathway, and simultaneously inhibiting the ERK and PAK/LIMK/cortactin signaling pathways, thereby inhibiting the EMT and metastasis of CRC. Rescue experiments showed that blocking the p130Cas and Rac1 activation could inhibit EMT induced by CSRP2 silencing. Conclusion: Our results suggest that the CSRP2/p130Cas/Rac1 axis can inhibit CRC aggressiveness and metastasis through the Hippo, ERK, and PAK signaling pathways. Therefore, CSRP2 may be a potential therapeutic target for CRC. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|