How does hif1a interfere the expression of glycolytic enzymes?
Hypoxia-inducible factor 1 alpha (HIF-1α) plays a pivotal role in the cellular response to low oxygen levels, particularly by modulating the expression of glycolytic enzymes, thereby adapting the cell's metabolic processes to hypoxic conditions. HIF-1α induces the over-expression and increased activity of several glycolytic protein isoforms that differ from those found in non-malignant cells, including key transporters and enzymes such as GLUT1, GLUT3, HKI, HKII, and LDH-A, among others. This enhanced glycolytic flux is crucial for tumor growth and survival under hypoxic conditions . Under hypoxic stress, eukaryotic cells, including cancer cells, shift their metabolic strategy from mitochondrial respiration to increased glycolysis, a process regulated at the transcriptional level by HIF-1α, which induces an increased expression of glycolytic enzymes . This regulatory mechanism is not only essential for maintaining bioenergetic homeostasis during hypoxia but also contributes to tumor survival and growth . Furthermore, HIF-1α's transcriptional activity is increased by hypoxic glycolysis, establishing a feed-forward mechanism that stimulates tumor growth . Interestingly, the regulatory effects of HIF-1α on glycolysis are not limited to cancer cells. For instance, in esophageal carcinoma cells, HIF-1α upregulates the expression of glycolytic enzymes such as hexokinase 2 (HK2) and pyruvate dehydrogenase kinase 1 (PDK1) under hypoxia, promoting glycolysis . Additionally, noncoding RNAs have been identified as regulators of HIF1A, influencing its ability to modulate glycolysis in hepatocellular carcinoma, further highlighting the complex regulatory networks involving HIF-1α . Moreover, HIF-1α's interaction with other cellular components, such as aldolase A (ALDOA), has been shown to significantly decrease glycolysis, HIF-1 activity, and cancer cell proliferation when blocked, suggesting potential therapeutic targets for inhibiting tumor growth . This intricate regulation of glycolytic enzymes by HIF-1α underscores its critical role in cellular adaptation to hypoxia, with significant implications for cancer metabolism and potential therapeutic interventions.
Answers from top 6 papers
| Papers (6) | Insight |
|---|---|
401 Citations | HIF-1α induces over-expression of specific glycolytic isoforms in cancer cells, altering enzyme kinetics and promoting survival pathways, ultimately enhancing tumor glycolytic flux and growth. |
| HIF-1α regulates glycolytic enzyme expression by inducing their transcription, influencing glucose uptake, and mediating cellular glucose metabolism, creating a mutual relationship between HIF-1α and glycolysis. | |
| HIF-1α upregulates glycolytic enzyme expression, promoting increased glycolytic flux during hypoxia, crucial for cellular energy maintenance under low oxygen conditions. | |
| HIF-1α upregulates glycolytic enzymes like HK2 and PDK1 under hypoxia, promoting increased glucose uptake and lactate production in esophageal carcinoma cells, enhancing glycolysis. | |
| HIF1α drives glycolytic enzyme expression in hypoxic tumors, creating a feed-forward mechanism that boosts glycolysis, HIF1α activity, and tumor growth, with aldolase A inhibition showing promising therapeutic potential. | |
| HIF1α drives glycolytic enzyme expression in hypoxic tumors, creating a feed-forward mechanism where increased glycolysis boosts HIF1α activity, promoting tumor growth. Aldolase A inhibition shows promise as a therapeutic target. |