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Published on: July 21, 2018
HPV18 oncoproteins driven expression of PKM2 reprograms HeLa cell metabolism to maintain aerobic glycolysis and
Gopinath Prakasam1, Mohammad Askandar Iqbal2, Anusha Srivastava3
1School of Life Sciences, Jawaharlal Nehru University, New Delhi, 110067 India.
Abstract:
The molecular basis of human papillomavirus (HPV)-mediated cellular immortalization and malignant transformation has illustrated an indispensable role of viral E6/E7-oncoproteins. However, the impact of viral-oncoproteins on the metabolic phenotype of cancer cells remains ambiguous. We showed silencing of HPV18-encoded E6/E7-oncoprotein significantly reduced glucose consumption, lactate production, ATP level and viability. Silencing of HPV18-encoded E6/E7 in HeLa cells significantly down-regulated expression and activity of HK1, HK2, LDHA, and LDHB. Interestingly, there was an increased pyruvate kinase activity due to switch in expression from PKM2 isoform to PKM1. The switch in favor of alternatively spliced isoform PKM1, was regulated by viral-E6/E7-oncoprotein by inhibiting the c-Myc/hnRNP-axis. Further, the near absence of the PKM1 protein despite an adequate amount of PKM1 mRNA in HeLa cells was due to its proteasomal degradation. Our results suggests HPV18-encoded E6/E7 driven preferential expression of PKM2 is essential to support aerobic glycolysis and cell proliferation.
Supplementary Information:
The online version contains supplementary material available at 10.1007/s13337-022-00776-w.
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