DYNLT3 overexpression induces apoptosis and inhibits cell growth and migration via inhibition of the Wnt pathway and EMT in cervical cancer

Abstract

The role of the dynein light chain Tctex-type 3 (DYNLT3) protein in the biological behavior of cervical cancer and its relative molecular mechanisms were investigated. Immunohistochemical staining was used to detect DYNLT3 protein expression in cervical cancer tissues. Cell proliferation and apoptosis rates and invasiveness and migratory capacities were determined by CCK-8 assays, BrdU staining assays and colony formation assays, fluorescence activated cell sorting (FACS), wound healing assays, and Transwell invasion assays of cervical cancer cells after DYNLT3 modulation. The expression levels of Wnt signaling pathway- and EMT-related proteins were examined by Western blotting. Furthermore, the effects of DYNLT3 on the tumorigenicity and metastasis of cervical cancer in nude mice were analyzed by performing immunohistochemistry, and we found that the expression level of the DYNLT3 protein was higher in human normal cervical tissues than in cervical cancer tissues. Overexpression of DYNLT3 obviously attenuated the proliferation, migration and invasion of CaSki and SiHa cells, and promoted cell apoptosis. Upregulation of DYNLT3 expression markedly decreased the expression of Wnt signaling pathway-related proteins (Dvl2, Dvl3, p-LRP6, Wnt3a, Wnt5a/b, Naked1, Naked2, β-catenin and C-Myc) and EMT-related proteins (N-cadherin, SOX2, OCT4, vimentin and Snail), and increased the expression of E-cadherin and Axin1. However, the opposite results were observed after down-regulation of DYNLT3 expression. Up-regulation of DYNLT3 expression significantly inhibited tumor growth in a nude mouse model, while downregulation of DYNLT3 showed the opposite results. In addition, the major metastatic site of cervical cancer cells in mice was the lung, and downregulation of DYNLT3 expression increased cancer metastasis in vivo. DYNLT3 exerted inhibitory effects on cervical cancer by inhibiting cell proliferation, migration and invasion, promoting cell apoptosis in vitro, and inhibiting tumor growth and metastasis in vivo, possibly by suppressing the Wnt signaling pathway and the EMT.

The role of DYNLT3 in breast cancer proliferation, migration, and invasion via epithelial‐to‐mesenchymal transition

“…Consistent with our experimental findings, Zhu et al 20 explored that DYNLT3 enhanced the migratory and invasive abilities of ovarian cancer. Zhang et al 23 also found that DYNLT3 regulates EMT-related proteins in cervical cancer. The EMT process in carcinogenesis is extremely complex, serving a pleiotropic function in the processes of cancer occurrence and metastasis.…”

“…26,27 DYNLT3 affect carcinogenesis might be related to the tumor types, exerting its oncogenic or tumor-suppressive role in a tissue-specific manner. 20,23 DYNLT3 was identified as an age-associated gene. 24 As a result, the present research aimed to discover the potential mechanism of DYNLT3 on breast cancer cell growth and development.…”

“…22 Another study also found that upregulation of DYNLT3 expression induced apoptosis and attenuated tumor metastasis in cervical cancer. 23 Notably, recent bioinformatics research has indicated that DYNLT3, as one of the aging-associated genes, was upregulated in the human mammary carcinoma. 24 Nevertheless, studies of DYNLT3 action in tumors are very limited, especially in terms of its function and specific mechanism on the occurrence and development of breast cancer are still indistinct.…”

OTX1 promotes tumorigenesis and progression of cervical cancer by regulating the Wnt signaling pathway

“…Wnt signaling pathway promotes tumor progression and metastasis in various types of cancer, such as gastric cancer, pancreatic cancer, lung cancer, and cervical cancer (24)(25)(26)(27)(28)(29). Previous studies have shown that the Wnt/β-catenin pathway is activated in numerous types of cancer, including cervical cancer (30-32).…”

“…Previous studies have shown that the Wnt/β-catenin pathway is activated in numerous types of cancer, including cervical cancer (30-32). Zhang et al (29) suggested that activation of Wnt signaling pathway significantly enhances cell viability and migration in cervical cancer. Inhibition of Wnt/β-catenin signaling pathway decreases cell viability and proliferation in ovarian cancer (33).…”