Junctional adhesion molecule-like protein promotes tumor progression via the Wnt/β-catenin signaling pathway in lung adenocarcinoma

Abstract

Background Lung adenocarcinoma (LUAD) is a heavy social burden worldwide. Because the mechanisms involved in LUAD remain unclear, the prognosis of LUAD remains poor. Consequently, it is urgent to investigate the potential mechanisms of LUAD. Junctional adhesion molecule-like protein (JAML), is recognized as a tumorigenesis molecule in gastric cancer. However, the role of JAML in LUAD is still unclear. Here we aimed to evaluate the role of JAML in LUAD. Methods qRT-PCR, Western blotting and immunohistochemistry were conducted to investigate the expression of JAML in LUAD tissues. JAML was knocked down and overexpressed in LUAD cells using transient transfection by siRNA and plasmids or stable transfection by lentivirus. Proliferation potential of LUAD cells were detected by Cell Counting Kit-8, EdU incorporation and Colony formation assay. Migration and invasion abilities of LUAD cells were determined by wound healing, transwell migration and invasion assays. Cell cycle and cell apoptosis were detected by flow cytometry. The effects of JAML in vivo were studied in xenograft tumor models. Western blotting was used to explore the molecular mechanisms of JAML function. In addition, rescue experiments were performed to verify the possible mechanisms. Results JAML expression was elevated in LUAD tissues compared with peritumor tissues, and this upregulation was positively related to pT and pTNM. Furthermore, both in vitro and in vivo, JAML silencing markedly repressed malignant behaviors of LUAD cells and vice versa. Knockdown of JAML also mediated cell cycle arrest at G0/G1 phase and promoted apoptosis in LUAD cells. Mechanistically, silencing JAML repressed the process of epithelial-mesenchymal transition by inactivating the Wnt/β-catenin pathway in LUAD cells. Effects of JAML can be rescued by Wnt/β-catenin pathway activator in A549 cells. Conclusions Our data reveal the oncogenic role of JAML in LUAD, indicating that JAML may be a predictive biomarker and novel therapeutic target for LUAD.

JAML overexpressed in colorectal cancer promotes tumour proliferation by activating the PI3K-AKT-mTOR signalling pathway

“…Survival analysis revealed that high expression of JAML predicted poor survival in patients with CRC. These results were also supported by previous studies on gastric cancer and lung adenocarcinoma tissues 14,15 . However, our study also showed that the expression of JAML was not correlated with T stage in patients with CRC, which may have been due to the bias that almost all patients in our study had T3 or T4 disease.…”

“…Our research group was the rst to nd that JAML was highly expressed in gastric cancer tissues and was also associated with poor prognosis 14 . Subsequently, Wu reported high expression of JAML in patients with lung adenocarcinoma 15 . However, the expression and the biological function of JAML in CRC remain unclear.…”

RPS24 Is Associated with a Poor Prognosis and Immune Infiltration in Hepatocellular Carcinoma

“…To further verify the biological function of RPS24, we found that inhibiting the expression of RPS24 in HCC cells could inhibit the growth of subcutaneous tumor tissue in vivo. In addition, we discovered that highly expressed RPS24 could significantly enrich multiple cancer-promoting signaling pathways, such as the E2F targets, Wnt/β-catenin signaling, G2M checkpoint, and MYC targets, which accelerated tumor cell mitosis [23][24][25]. Furthermore, we found that the RPS24 hypermethylation or hypomethylation status affected the cancer cells' malignant characteristics.…”

Wnt/β-catenin signaling in the development and therapeutic resistance of non-small cell lung cancer

“…β-Catenin protein expression is also upregulated by FOXH1 [ 123 ], LRP8 [ 124 ], CBX4 [ 125 ], SMEK1 [ 126 ], JAML [ 127 ], ERCC6L [ 128 ], NOVA1 [ 129 ], SETDB1 [ 130 ], HMGB1 [ 131 ] and DEPDC1B [ 132 ] (Table 2 ), though the underlying molecular mechanism remains elusive. Additional regulators specifically mediate the level of active (i.e., unphosphorylated at Ser33/Ser37/Thr41) β‐catenin.…”