Investigation of the effect of HIF1α and HIF1ß' on collective invasion in lung cancer in hypoxic condition

Hypoxic condition is a microenvironmental condition that occurs when cells are exposed to insufficient amounts of oxygen. In cancerous cells, as the tumor grows, the cells in the center, which are not exposed to nutrients and oxygen, are exposed to hypoxia. HIF1α and HIF1ß, known as hypoxia-induced factors (HIFs), directly affect tumor biology by making a series of regulations on gene expression, especially under hypoxic conditions. Together with the hypoxic environment, this condition is known to be of critical importance in the progression and metastasis of tumors. The process involved in the spread of primary tumor cells to both the immediate environment and distant organs is complex. Research in this field has shown that in cancer spread, cells can spread alone or collectively as a group by inducing the epithelial-mesenchymal transition (EMT) process. On the other hand, under hypoxia, collectively migrating cells may also undergo collective to amoeboid transition (CAT) in a HIF-1α-dependent manner. In the light of this information, the effects of HIF1α and HIF1ß on some gene and protein expressions and cell migration of lung cancer cells under hypoxic conditions were examined by transfecting siRNA in extracellular A549 cells. It has been shown that collective invasion is greater in normoxia than in hypoxia, where cell-cell bonds are weakened, and at 24 hours in hypoxia, invasion in the HIF1α silenced condition has been shown to be more collective cell migration than in the control. When HIF1ß was silenced, HER2 expression decreased significantly in normoxic conditions and increased significantly in hypoxic conditions. In hypoxic conditions, along with the increase in Glut-1 mRNA expression, an increase in VEGF expression, which provides angiogenesis, was observed, while a decrease was observed in the HIF1α silenced condition in hypoxia compared to the hypoxia control.