Extracellular Pyruvate Kinase M2 regulates tumor angiogenesis
نویسندگان
چکیده
Pyruvate kinase M2 (PKM2) has been studied for decades on its role in cancer metabolism. Re-cently, PKM2 is highlighted again for its new function: promoting gene transcription by acting as a pro-tein kinase. Moreover, the PKM2 levels in patient circulation have been used as a diagnostic marker formany types of cancers. However, it remains unclear whether PKM2 in blood circulation has any physio-logical or pathological function. In my dissertation, I demonstrate that PKM2 released from cancer cellsfacilitates tumor growth by promoting tumor angiogenesis. Our experiments show that PKM2 promotes endothelial cell proliferation, migration and survival. Only the dimeric PKM2, not the tetrameric PKM2possesses the activity in angiogenesis promotion. Our results further indicate that PKM2 regulates angi-ogenesis by integrin αvβ3 activation and integrin redistribution. I also found that PKM2 enhances drugresistance of cancer cells expressing integrin αvβ3. INDEX WORDS: Pyruvate kinase M2, Cancer, Angiogenesis, Integrin EXTRACELLULAR PYRUVATE KINASE M2 REGULATES TUMOR ANGIOGENESIS
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