Microarray and qRT-PCR analyses revealed that ten of 18 ABC transporter genes were significantly (P<0.05) upregulated in the CD133(+) subpopulation, while inhibition of ABC activity increased sensitivity, suggesting a mechanism for increased drug resistance of CD133(+) cells.
For example, gene mutations in some types of cancers can lead to constitutive activation of Nrf2 and give the tumor cells growth advantages and increased drug resistance.
Microarray and qRT-PCR analyses revealed that ten of 18 ABC transporter genes were significantly (P<0.05) upregulated in the CD133(+) subpopulation, while inhibition of ABC activity increased sensitivity, suggesting a mechanism for increased drug resistance of CD133(+) cells.
The LIN28B-long isoform-expressing cells demonstrated increased drug resistance to 5-fluorouracil and cisplatin through the upregulation of ERCC1, a DNA repair gene, in a <i>LET-7</i>-dependent manner.
Doxorubicin-resistant BT-549 (BT-549<sup>r</sup>DOX<sup>20</sup>) and 5-Fluorouracil-resistant MDA-MB-468 (MDA-MB-468<sup>r</sup>5-FU<sup>2000</sup>) cells were chosen for further analysis with the autophagy inhibitor Bafilomycin A1 and lentiviral depletion of ATG5, indicating that enhanced cytoprotective autophagy partially contributes to increased drug resistance and cell survival.
The LIN28B-long isoform-expressing cells demonstrated increased drug resistance to 5-fluorouracil and cisplatin through the upregulation of ERCC1, a DNA repair gene, in a <i>LET-7</i>-dependent manner.
Furthermore, mechanistic investigation revealed that NAC1increased drug resistance via inducing homeobox A9 (HOXA9) expression, and that knockdown of HOXA9 abrogated NAC1‑induced drug resistance.
Analysis of cell viability in the control and DKK4 over-expressing cell lines, following treatment with 5-fluorouracil (5-Fu), YN968D1 or both, indicated that DKK4 over-expressing cells exhibit increased drug resistance.
Furthermore, mechanistic investigation revealed that NAC1increased drug resistance via inducing homeobox A9 (HOXA9) expression, and that knockdown of HOXA9 abrogated NAC1‑induced drug resistance.
Contrary to our hypothesis, ablation of Glut1 attenuated apoptosis and increased drug resistance via upregulation of p-Akt/p-GSK-3β (Ser9)/β-catenin/survivin.
Contrary to our hypothesis, ablation of Glut1 attenuated apoptosis and increased drug resistance via upregulation of p-Akt/p-GSK-3β (Ser9)/β-catenin/survivin.
Altogether, our data suggest that low Teneurin-4 expression provides a growth advantage to cancer cells and marks an undifferentiated state characterized by increased drug resistance and clinical aggressiveness.