American Association for Cancer Research
00085472can120448-sup-can_12-0448_fig5_pdf_41k.pdf (40.89 kB)

Supplementary Figure 5 from Caveolin-1 Increases Aerobic Glycolysis in Colorectal Cancers by Stimulating HMGA1-Mediated GLUT3 Transcription

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journal contribution
posted on 2023-03-30, 21:11 authored by Tae-Kyu Ha, Nam-Gu Her, Min-Goo Lee, Byung-Kyu Ryu, Jin-Hee Lee, Jikhyon Han, Seong-In Jeong, Min-Ju Kang, Nam-Hoon Kim, Hyo-Jong Kim, Sung-Gil Chi

PDF file- 41K, A dose-associated decrease in GLUT3 promoter activity by si-CAV1 transfection



Caveolin-1 (CAV1) acts as a growth suppressor in various human malignancies, but its expression is elevated in many advanced cancers, suggesting the oncogenic switch of its role during tumor progression. To understand the molecular basis for the growth-promoting function of CAV1, we characterized its expression status, differential roles for tumor growth, and effect on glucose metabolism in colorectal cancers. Abnormal elevation of CAV1 was detected in a substantial fraction of primary tumors and cell lines and tightly correlated with promoter CpG sites hypomethylation. Depletion of elevated CAV1 led to AMPK activation followed by a p53-dependent G1 cell-cycle arrest and autophagy, suggesting that elevated CAV1 may contribute to ATP generation. Furthermore, CAV1 depletion downregulated glucose uptake, lactate accumulation, and intracellular ATP level, supporting that aerobic glycolysis is enhanced by CAV1. Consistently, CAV1 was shown to stimulate GLUT3 transcription via an HMGA1-binding site within the GLUT3 promoter. HMGA1 was found to interact with and activate the GLUT3 promoter and CAV1 increased the HMGA1 activity by enhancing its nuclear localization. Ectopic expression of HMGA1 increased glucose uptake, whereas its knockdown caused AMPK activation. In addition, GLUT3 expression was strongly induced by cotransfection of CAV1 and HMGA1, and its overexpression was observed predominantly in tumors harboring high levels of CAV1 and HMGA1. Together, these data show that elevated CAV1 upregulates glucose uptake and ATP production through HMGA1-mediated GLUT3 transcription, suggesting that CAV1 may render tumor cells growth advantages by enhancing aerobic glycolysis. Cancer Res; 72(16); 4097–109. ©2012 AACR.

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