Dataset Information

Overexpression of ANLN in lung adenocarcinoma is associated with metastasis.

ABSTRACT:

Background

ANLN has been identified as an actin-binding protein and previous studies have suggested that ANLN is associated with actin cytoskeletal dynamics. Lung adenocarcinoma is a poor prognosis tumor. Metastasis is a very common complication and is regarded as the main cause for an unsatisfactory treatment outcome. Whether ANLN is involved in the metastasis of lung adenocarcinoma is unknown.

Methods

We performed immunohistochemical staining and analyzed the correlation between the expression level and pathological parameters. We tested the migration and invasion of A549 and PC9 cell after interference with ANLN expression by Transwell and scratch wound healing assays. Protein expression of E-cadherin, vimentin and N-cadherin were detected using Western blotting and immunofluorescence staining. The same experiment was also tested after overexpression of ANLN.

Results

The metastasis of patients with high expression of ANLN was significantly more than that of patients with low expression of ANLN. In vitro, after interfering with ANLN expression, E-cadherin and vimentin expression were increased and N-cadherin expression was decreased in A549 and PC9 cells. Migration and invasion ability of A549 and PC9 cells were decreased,vice versa.

Conclusion

Our study suggests that the expression of ANLN in lung adenocarcinoma is associated with metastasis of cancer cells. ANLN may be involved in the metastasis of lung adenocarcinoma by promoting epithelial mesenchymal transformation of tumor cells.

SUBMITTER: Xu J

PROVIDER: S-EPMC6669805 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Publications

Overexpression of ANLN in lung adenocarcinoma is associated with metastasis.

Xu Jie J Zheng Hong H Yuan Shuai S Zhou Bodong B Zhao Weipeng W Pan Yuan Y Qi Daliang D

Thoracic cancer 20190703 8

<h4>Background</h4>ANLN has been identified as an actin-binding protein and previous studies have suggested that ANLN is associated with actin cytoskeletal dynamics. Lung adenocarcinoma is a poor prognosis tumor. Metastasis is a very common complication and is regarded as the main cause for an unsatisfactory treatment outcome. Whether ANLN is involved in the metastasis of lung adenocarcinoma is unknown.<h4>Methods</h4>We performed immunohistochemical staining and analyzed the correlation between ...[more]

PMID: 31268619

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Project description:p62 protein has been implicated in bone metastasis and is a multifunctional adaptor protein usually correlated with autophagy. Herein, we investigated p62 expression and its prognostic significance in bone metastasis of lung adenocarcinoma, and analyzed whether the mechanism involved depends on autophagy. mRNA and protein expression of p62, LC3B and Beclin 1 were detected by reverse transcription-quantitative PCR and western blotting, respectively, in fresh bone metastasis tissues (n=6 cases) and normal cancellous bone tissues (n=3 cases). The association between p62 and LC3B expression and patient prognosis was subsequently analyzed in 62 paraffin-embedded bone metastasis specimens by immunohistochemistry assay. Small interfering RNA (siRNA) was employed to downregulate p62 expression in SPC-A-1 and A549 cells. Cell proliferation and migration ability were tested by CCK8, CCF and Transwell assays respectively. Autophagy was induced by Rapamycin or inhibited by Atg 7 knockout/Chloroquine in A549 cells and p62 and LC3II/I expression were analyzed. After subcutaneous inoculation or intracardial injection of A549 cells into nude mice, the effect of p62 downregulation in vivo was analyzed by histopathological examination. The results showed that p62, LC3B and Beclin 1 mRNA and protein were all overexpressed in bone metastasis tissues (all P<0.01). Patient samples with high p62 expression levels were significantly associated with more bone lesions (>3), shorter overall survival rates and shorter progression free survival rates compared with patients having lower p62 expression (P=0.014, P=0.003, P=0.048, respectively). Cox regression analysis identified p62 expression as an independent prognostic indicator of overall survival of patients with bone metastasis (P=0.007). In vitro p62 downregulation inhibited SPC-A-1 and A549 cells migration but had no effect on cell proliferation. After autophagy induction or inhibition, p62 expression involved in autophagy flux and changed inconsistently according to the switch of LC3I to LC3II in different autophagy conditions. In vivo p62 downregulation had no effect on growth of subcutaneous tumor. Lung or bone metastasis lesion was not found in all mice model. These findings suggested that p62 overexpression promotes tumor cell invasion out of LC3-dependent autophagy, which could be used a potential prognostic biomarker and therapeutic target for bone metastasis of lung adenocarcinoma.

Dataset Information

Overexpression of ANLN in lung adenocarcinoma is associated with metastasis.

Background

Methods

Results

Conclusion

Publications

Overexpression of ANLN in lung adenocarcinoma is associated with metastasis.

Similar Datasets

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