BTBD7 Downregulates E-Cadherin and Promotes Epithelial-Mesenchymal Transition in Lung Cancer

Abstract

Metastasis is the leading cause of lung cancer-associated death. Downregulated expression of E-cadherin followed by epithelial-mesenchymal transition (EMT) is critical for metastasis initiation in lung cancer. BTBD7 plays essential roles in lung cancer metastasis, but the mechanisms remain unknown. This study aimed to investigate the relationship between BTBD7 and E-cadherin in lung cancer and explore the role of BTBD7 in EMT. Fresh lung cancer and paracancer tissue specimens were collected from 30 patients, and the expression of BTBD7, E-cadherin, N-cadherin, fibronectin, and vimentin was analyzed by qRT-PCR, western blotting, and immunohistochemistry. A549 and HBE cells were cultured and treated with TGF-β1 for 72 h to induce EMT. Western blotting and qRT-PCR were performed to evaluate the expression of BTBD7, E-cadherin, N-cadherin, fibronectin, and vimentin. Then, A549 cells were treated separately with the BTBD7-ENTER plasmid, BTBD7-siRNA, and paclitaxel. After TGF-β1-induced EMT, the abovementioned markers were analyzed by western blotting and qRT-PCR. Wound healing assays were applied to assess the migration ability of cells in different groups. For animal experiments, A549 cells transfected with the BTBD7-ENTER plasmid were transplanted into BALB/c nude mice. After 4 weeks, all nude mice were sacrificed, and tumor tissues were harvested for qRT-PCR, western blot, and immunohistochemical analyses of the abovementioned markers. All experimental results showed that the levels of BTBD7, N-cadherin, fibronectin, and vimentin were increased in lung cancer tissues and cells, while the E-cadherin level was decreased. Transfection experiments showed that BTBD7 inhibited E-cadherin expression and enhanced EMT. Moreover, the migration capacity of lung cancer cells was increased by the high level of BTBD7. We concluded that BTBD7 is highly expressed during lung cancer development and metastasis and can inhibit the expression of E-cadherin and promote EMT in lung cancer. BTBD7 may thus be a therapeutic target for lung cancer.

Association of the Epithelial–Mesenchymal Transition (EMT) with Cisplatin Resistance

“…Thus, modulation of EMT can also be of importance in treatment of non-cancerous diseases [125][126][127]. It has been shown that E-cadherin downregulation may be associated with the development of a number of cancers such as breast cancer [128], lung cancer [129], skin cancer [130], and GC [131]. This can be related to the EMT mechanism.…”

Lung CSC‐derived exosomal miR‐210‐3p contributes to a pro‐metastatic phenotype in lung cancer by targeting FGFRL1

“…as the main proteins associated with cell migration. 27 MMP-9 and MMP-1 are proteolytic enzymes that facilitate cell invasion by degrading extracellular matrix, which leads to metastasis. 28 Previous reports indicated that lung CSCs were endowed with EMT characteristics and increased risk for metastasis.…”

LncRNA MEG3 inhibits non‑small cell lung cancer via interaction with DKC1 protein

“…Lung cancer is considered the most common type of tumor and is a predominant cause of cancer-associated mortality in China ( 1 – 3 ). Currently, more than 1.5 million cases of mortality are reported from lung carcinomas annually, and the 5-year survival rate is only 17% ( 1 , 4 ). Early stage symptoms of lung cancer are atypical and the majority of the different types of lung cancer are not detected until advanced stage.…”