Metastasis is the major cause of high mortality in lung cancer. Exploring the underlying mechanisms of metastasis thus holds promise for identifying new therapeutic strategies that may enhance survival.
Methods:
We applied quantitative mass spectrometry to compare protein expression profiles between primary and metastatic lung cancer cells whilst investigating metastasis-related molecular features.
Results:
We discovered that BCAT1, the key enzyme in branched-chain amino acid metabolism, is overexpressed at the protein level in metastatic lung cancer cells, as well as in metastatic tissues from lung cancer patients. Analysis of transcriptomic data available in the TCGA database revealed that increased BCAT1 transcription is associated with poor overall survival of lung cancer patients. In accord with a critical role in metastasis, shRNA-mediated knockdown of BCAT1 expression reduced migration of metastatic cells
in vitro
and the metastasis of these cells to distal organs in nude mice. Mechanistically, high levels of BCAT1 depleted α-ketoglutarate (α-KG) and promoted expression of SOX2, a transcription factor regulating cancer cell stemness and metastasis.
Conclusion:
Our findings suggest that BCAT1 plays an important role in promoting lung cancer cell metastasis, and may define a novel pathway to target as an anti-metastatic therapy.
With the increasing number of female senior executives, the relationship between female senior executives and corporate innovation behaviors has attracted widespread attention, but few works have studied the influences of female CEOs on innovation behaviors and their mechanisms. This paper studies the relationship between CEO's gender and the selection of corporate innovation behaviors, as well as the regulating effect of gender culture on the relationship between them. It was discovered in the studies that (1) if compared with male CEOs, female CEOs have significantly promoted both incremental innovation behaviors and radical innovation behaviors; (2) gender culture has positively regulated the relationship between CEO's gender and corporate incremental innovation behaviors, yet the regulating effect of gender culture on the relationship between CEO's gender and corporate radical innovation behaviors is not significant. Thus, the government needs to further foster a gender culture with gender equality, and actively promote the positive effect of female CEOs in corporate innovations.
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