p27Kip1 mediates addiction of ovarian cancer cells to MYCC (c-MYC) and their dependence on MYC paralogs.

The Journal of Biological Chemistry
Tulsiram PrathapamG Steven Martin

Abstract

The MYCC (c-MYC) gene is amplified in 30-60% of human ovarian cancers. We assessed the functional significance of MYCC amplification by siRNA inhibition of MYCC or MYC paralogs in a panel of ovarian cancer cell lines expressing varying levels of MYCC. Inactivation of MYCC inhibited cell proliferation and induced replicative senescence only in lines with amplified MYCC, indicating that these cells are addicted to continued MYCC overexpression. In contrast, siRNA knockdown of all three MYC isoforms inhibited proliferation of MYCC non-amplified ovarian cancer cells without inducing replicative senescence, and did not inhibit the proliferation of telomerase-immortalized ovarian surface epithelial cells. The arrest induced by MYCC knockdown was accompanied by an increase in the level of the Cdk inhibitor p27(Kip1) and a decrease in cyclin A expression and Cdk2 activity, and could be reversed by RNAi knockdown of p27(Kip1) or Rb, or by overexpression of cyclin A/Cdk2. The arrest induced by knockdown of all three MYC isoforms could similarly be reversed by p27(Kip1) knockdown. Our findings indicate that the addiction of MYCC-amplified ovarian cancer cells to MYCC differs from the dependence of MYCC non-amplified cancer cells on MYC pa...Continue Reading

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Citations

May 19, 2016·Oncotarget·Chantelle D HudsonNorbert Avril
Jan 11, 2020·International Journal of Oncology·Hualei BuBeihua Kong
Jul 31, 2019·JNCI Cancer Spectrum·MoonSun JungMichelle J Henderson
Aug 1, 2015·Molecular Cancer Therapeutics·Jeyshka M Reyes-GonzálezPablo E Vivas-Mejía
Mar 16, 2021·Frontiers in Oncology·Jeyshka M Reyes-González, Pablo E Vivas-Mejía
Oct 2, 2021·Journal of Ovarian Research·Meysam Moghbeli
Oct 15, 2021·Oncogene·Dongqing HuangAmanda G Paulovich

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