Correction to: Inhibition of mTORC1 through ATF4-induced REDD1 and Sestrin2 expression by Metformin

Jang, Se Kyeong; Hong, Sung Eun; Lee, Da Hee; Kim, Ji Young; Kim, Ji Yea; Ye, Sang Kyu; Hong, Jungil; Park, In-Cheol; Jin, Hyeon Ok

doi:10.1186/s12885-021-08584-z

Cited by 1 publication

(1 citation statement)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These findings suggest that inhibiting mTORC1/S6K1 can sensitize cells to the effects of lapatinib and/or duloxetine. ATF4 (activating transcription factor 4) is an essential transcription factor that mediates the expression of the mTORC1 upstream regulatory protein REDD1 (regulated in development and DNA damage responses) [22,40]. Thus, we investigated whether ATF4/REDD1 is involved in the inhibition of mTORC1 activity by duloxetine and/or lapatinib.…”

Section: Discussionmentioning

confidence: 99%

Duloxetine enhances the sensitivity of non-small cell lung cancer cells to EGFR inhibitors by REDD1-induced mTORC1/S6K1 suppression

Jang

2024

Am J Cancer Res

View full text Add to dashboard Cite

Although epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have been effective targeted therapies for non-small cell lung cancer (NSCLC), most advanced NSCLC inevitably develop resistance to these therapies. Combination therapies emerge as valuable approach to preventing, delaying, or overcoming disease progression. Duloxetine, an antidepressant known as a serotonin-noradrenaline reuptake inhibitor, is commonly prescribed for the treatment of chemotherapy-induced peripheral neuropathy. In the present study, we investigated the combined effects of duloxetine and EGFR-TKIs and their possible mechanism in NSCLC cells. Compared with either monotherapy, the combination of duloxetine and EGFR-TKIs leads to synergistic cell death. Mechanistically, duloxetine suppresses 70-kDa ribosomal protein S6 kinase 1 (p70S6K1) activity through mechanistic target of rapamycin complex 1 (mTORC1), and this effect is associated with the synergistic induction of cell death of duloxetine combined with EGFR-TKIs. More importantly, activating transcription factor 4 (ATF4)-induced regulated in development and DNA damage response 1 (REDD1) is responsible for the suppression of mTORC1/S6K1 activation. Additionally, we found that the combination effect was significantly attenuated in REDD1 knockout NSCLC cells. Taken together, our findings reveal that the ATF4/REDD1/mTORC1/S6K1 signaling axis, as a novel mechanism, is responsible for the synergistic therapeutic effect of duloxetine with EGFR-TKIs. These results suggest that combining EGFR-TKIs with duloxetine appears to be a promising way to improve EGFR-TKI efficacy against NSCLC.

show abstract

Section: Discussionmentioning

confidence: 99%

Duloxetine enhances the sensitivity of non-small cell lung cancer cells to EGFR inhibitors by REDD1-induced mTORC1/S6K1 suppression

Jang

2024

Am J Cancer Res

View full text Add to dashboard Cite

show abstract

Correction to: Inhibition of mTORC1 through ATF4-induced REDD1 and Sestrin2 expression by Metformin

Cited by 1 publication

References 1 publication

Duloxetine enhances the sensitivity of non-small cell lung cancer cells to EGFR inhibitors by REDD1-induced mTORC1/S6K1 suppression

Duloxetine enhances the sensitivity of non-small cell lung cancer cells to EGFR inhibitors by REDD1-induced mTORC1/S6K1 suppression

Contact Info

Product

Resources

About