LRIG3 represses cell motility by inhibiting slug via inactivating ERK signaling in human colorectal cancer.
Metastasis is responsible for 90% of colorectal cancer (CRC)-related deaths. In the present study, we identified a novel key regulator of CRC metastasis, leucine-rich repeats and immunoglobulin-like domains protein 3 (LRIG3), which was significantly decreased in CRC tissues and cell lines. Downregulation of LRIG3 was attributed to copy number loss and promoter hypermethylation. Low LRIG3 expression was positively correlated with metastatic clinical features and shorter survival time. Functional experiments showed that knockout of LRIG3 markedly enhanced CRC cell migration and invasion ability, whereas reintroduction of LRIG3 exerted the opposite effects. Regarding the mechanism, LRIG3 could facilitate the binding of DUSP6 to ERK1/2, resulting in the dephosphorylation of ERK1/2 and subsequently downregulation of slug, an epithelial-to-mesenchymal transition trigger, thereby constraining CRC cell motility. Importantly, LRIG3 expression was strongly negatively correlated with slug or p-ERK1/2 expression in CRC tissues. Collectively, our data suggest that LRIG3 is a novel suppressor of CRC metastasis, reactivation of LRIG3 may be a promising therapeutic approach for metastatic CRC patients.
['Zeng|Kaixuan|K|', 'Chen|Xiaoxiang|X|', 'Xu|Mu|M|', 'Liu|Xiangxiang|X|', 'Li|Chenmeng|C|', 'Xu|Xueni|X|', 'Pan|Bei|B|', 'Qin|Jian|J|', 'He|Bangshun|B|', 'Pan|Yuqin|Y|', 'Huiling|Sun|S|', 'Xu|Tao|T|', 'Wang|Shukui|S|0000-0001-6972-2587']
D000368:Aged D017209:Apoptosis D014408:Biomarkers, Tumor D002465:Cell Movement D049109:Cell Proliferation D015179:Colorectal Neoplasms D005260:Female D015972:Gene Expression Regulation, Neoplastic D006801:Humans D008297:Male D008565:Membrane Proteins D019950:Mitogen-Activated Protein Kinase 1 D048052:Mitogen-Activated Protein Kinase 3 D010766:Phosphorylation D011379:Prognosis D015398:Signal Transduction D000071250:Snail Family Transcription Factors D015996:Survival Rate D014407:Tumor Cells, Cultured
LRIG3 ERK signaling colorectal cancer metastasis EMT