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USP44 suppresses proliferation and enhances apoptosis in colorectal cancer cells by inactivating the Wnt/?-catenin pathway via Axin1 deubiquitination.

ABSTRACT: Colorectal cancer (CRC) is the leading cause of cancer death, and its 5-year survival rate remains unsatisfactory. Recent studies have revealed that ubiquitin-specific protease 44 (USP44) is a cancer suppressor or oncogene depending on the type of neoplasm. However, its role in CRC remains unclear. Here, we found that the USP44 expression level was markedly decreased in CRC, and USP44 overexpression inhibited proliferation while enhancing apoptosis in CRC cells, suggesting that USP44 is a cancer suppressor in CRC. We then investigated if USP44 functioned through regulating the Wnt/?-catenin pathway. We found that USP44 overexpression increased the Axin1 protein while decreasing ?-catenin, c-myc, and cyclin D1 proteins, suggesting that USP44 inhibited the activation of the Wnt/?-catenin pathway. Moreover, we found that two Wnt/?-catenin activators, LiCl and SKL2001, both attenuated oeUSP44-mediated proliferation and apoptosis in CRC cells. Collectively, these data points indicated that USP44 inhibited proliferation while promoting apoptosis in CRC cells by inhibiting the Wnt/?-catenin pathway. Interestingly, we observed that USP44 overexpression did not affect the Axin1 mRNA level. Further study uncovered that USP44 interacted with Axin1 and reduced the ubiquitination of Axin1. Furthermore, Axin1 knock-down abolished the effects of oeUSP44 on proliferation, apoptosis, and Wnt/?-catenin activity in CRC cells. Taken together, this study demonstrates that USP44 inhibits proliferation while enhancing apoptosis in CRC cells by inactivating the Wnt/?-catenin pathway via Axin1 deubiquitination. USP44 is a cancer suppressor in CRC and a potential target for CRC therapy.

SUBMITTER: Huang T

PROVIDER: S-EPMC7496820 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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USP44 suppresses proliferation and enhances apoptosis in colorectal cancer cells by inactivating the Wnt/β-catenin pathway via Axin1 deubiquitination.

Huang Tong T Zhang Qingquan Q Ren Wei W Yan Bing B Yi Liang L Tang Tielun T Lin Hai H Zhang Yongjiu Y

Cell biology international 20200421 8

Colorectal cancer (CRC) is the leading cause of cancer death, and its 5-year survival rate remains unsatisfactory. Recent studies have revealed that ubiquitin-specific protease 44 (USP44) is a cancer suppressor or oncogene depending on the type of neoplasm. However, its role in CRC remains unclear. Here, we found that the USP44 expression level was markedly decreased in CRC, and USP44 overexpression inhibited proliferation while enhancing apoptosis in CRC cells, suggesting that USP44 is a cancer ...[more]

PMID: 32285989

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Project description:Purpose:FAM110B is a member of the FAM110 family (family with sequence similarity 110), which is a component of the centrosome associated proteins. Previous studies have shown that FAM110B may be involved in the process of cell cycle and may play a role in carcinogenesis and tumor progression. Using an online database, we found that FAM110B may predict favorable prognosis in non-small cell lung cancer (NSCLC). Therefore, the role of FAM110B playing in NSCLC needs to be further investigated. Patients and Methods:Online databases and immunohistochemistry were used to predict the expression and prognostic value of FAM110B in NSCLC samples. Immunofluorescence staining was used to investigate the subcellular distribution of FAM110B. Western blot, MTT, colony formation, and matrigel invasion assay were used to detect the expression and the effect of FAM110B on mediating proliferation and invasion in NSCLC cell lines. Results:In this study, immunohistochemistry results showed that FAM110B expression significantly correlated with early TNM staging (P=0.020) and negative regional lymph node metastasis (P=0.006). Kaplan-Meier survival analysis found that the median survival time of patients with positive FAM110B expression (56.181±2.348 months) was significantly longer than those with negative FAM110B expression (47.701±2.997 months, P=0.024). Moreover, overexpression of FAM110B inhibited the proliferation and invasion of A549, H1299, and LK2 cell lines. Conversely, FAM110B RNAi exerted opposite effects in the above cell lines. Furthermore, FAM110B overexpression downregulated the active ?-catenin, phosphorylation of GSK-3? (p-GSK-3?), cyclin B1, cyclin D1, MMP2, and MMP7, and upregulated the phosphorylation of ?-catenin (p-?-catenin) in A549 and H1299 cells. Besides, the FAM110B-induced depressions of p-GSK-3? and active ?-catenin were reversed after being treated with Wnt/?-catenin inhibitor, XAV-939. Conclusion:In summary, our results demonstrated that the overexpression of FAM110B restricts the proliferation and invasion of NSCLC cells by inhibiting Wnt/?-catenin signaling. Our study reveals the antitumor function of FAM110B in NSCLC and indicates that FAM110B is a potential therapeutic target.

Dataset Information

USP44 suppresses proliferation and enhances apoptosis in colorectal cancer cells by inactivating the Wnt/?-catenin pathway via Axin1 deubiquitination.

Publications

USP44 suppresses proliferation and enhances apoptosis in colorectal cancer cells by inactivating the Wnt/β-catenin pathway via Axin1 deubiquitination.

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