The Impact of Pdcd4, a Translation Inhibitor, on Drug Resistance

Overview

Journal Pharmaceuticals (Basel)

Publisher MDPI

Specialty Chemistry

Date 2024 Oct 26

PMID 39459035

Authors

Qing Wang

Hsin-Sheng Yang

Affiliations

Soon will be listed here.

Abstract

Programmed cell death 4 (Pdcd4) is a tumor suppressor, which has been demonstrated to efficiently suppress tumorigenesis. Biochemically, Pdcd4 binds with translation initiation factor 4A and represses protein translation. Beyond its role in tumor suppression, growing evidence suggests that Pdcd4 enhances the chemosensitivity of several anticancer drugs. To date, numerous translational targets of Pdcd4 have been identified. These targets govern important signal transduction pathways, and their attenuation may improve chemosensitivity or overcome drug resistance. This review will discuss the signal transduction pathways regulated by Pdcd4 and the potential mechanisms through which Pdcd4 enhances chemosensitivity or counteracts drug resistance.

References

Liu L, Zhou X, Qian G, Shi X, Fang J, Jiang B . AKT1 amplification regulates cisplatin resistance in human lung cancer cells through the mammalian target of rapamycin/p70S6K1 pathway. Cancer Res. 2007; 67(13):6325-32. DOI: 10.1158/0008-5472.CAN-06-4261. View

Jiang Z, Li L, Hou Z, Liu W, Wang H, Zhou T . LncRNA HAND2-AS1 inhibits 5-fluorouracil resistance by modulating miR-20a/PDCD4 axis in colorectal cancer. Cell Signal. 2019; 66:109483. DOI: 10.1016/j.cellsig.2019.109483. View

Wu Y, Zhu X, Shen R, Huang J, Xu X, He S . miR-182 contributes to cell adhesion-mediated drug resistance in multiple myeloma via targeting PDCD4. Pathol Res Pract. 2019; 215(11):152603. DOI: 10.1016/j.prp.2019.152603. View

Yang H, Cho M, Zakowicz H, Hegamyer G, Sonenberg N, Colburn N . A novel function of the MA-3 domains in transformation and translation suppressor Pdcd4 is essential for its binding to eukaryotic translation initiation factor 4A. Mol Cell Biol. 2004; 24(9):3894-906. PMC: 387765. DOI: 10.1128/MCB.24.9.3894-3906.2004. View

Schaller M . Cellular functions of FAK kinases: insight into molecular mechanisms and novel functions. J Cell Sci. 2010; 123(Pt 7):1007-13. DOI: 10.1242/jcs.045112. View

Fehler O, Singh P, Haas A, Ulrich D, Muller J, Ohnheiser J . An evolutionarily conserved interaction of tumor suppressor protein Pdcd4 with the poly(A)-binding protein contributes to translation suppression by Pdcd4. Nucleic Acids Res. 2014; 42(17):11107-18. PMC: 4176178. DOI: 10.1093/nar/gku800. View

Fang J, Meng Q, Vogt P, Zhang R, Jiang B . A downstream kinase of the mammalian target of rapamycin, p70S6K1, regulates human double minute 2 protein phosphorylation and stability. J Cell Physiol. 2006; 209(2):261-5. DOI: 10.1002/jcp.20749. View

Xue C, Gu X, Li G, Bao Z, Li L . Expression and Functional Roles of Eukaryotic Initiation Factor 4A Family Proteins in Human Cancers. Front Cell Dev Biol. 2021; 9:711965. PMC: 8640450. DOI: 10.3389/fcell.2021.711965. View

Kearney A, Cooke K, Norris D, Zadoorian A, Krycer J, Fazakerley D . Serine 474 phosphorylation is essential for maximal Akt2 kinase activity in adipocytes. J Biol Chem. 2019; 294(45):16729-16739. PMC: 6851323. DOI: 10.1074/jbc.RA119.010036. View

10.

Zhang Y, Wang Q, Chen L, Yang H . Inhibition of p70S6K1 Activation by Pdcd4 Overcomes the Resistance to an IGF-1R/IR Inhibitor in Colon Carcinoma Cells. Mol Cancer Ther. 2015; 14(3):799-809. PMC: 4456303. DOI: 10.1158/1535-7163.MCT-14-0648. View

11.

Ajzashokouhi A, Bostan H, Jomezadeh V, Hayes A, Karimi G . A review on the cardioprotective mechanisms of metformin against doxorubicin. Hum Exp Toxicol. 2019; 39(3):237-248. DOI: 10.1177/0960327119888277. View

12.

Cmarik J, Min H, Hegamyer G, Zhan S, Kulesz-Martin M, Yoshinaga H . Differentially expressed protein Pdcd4 inhibits tumor promoter-induced neoplastic transformation. Proc Natl Acad Sci U S A. 1999; 96(24):14037-42. PMC: 24186. DOI: 10.1073/pnas.96.24.14037. View

13.

Wang Q, Zhu J, Wang Y, Dai Y, Wang Y, Wang C . Tumor suppressor Pdcd4 attenuates Sin1 translation to inhibit invasion in colon carcinoma. Oncogene. 2017; 36(45):6225-6234. PMC: 5680133. DOI: 10.1038/onc.2017.228. View

14.

Fu W, Hall M . Regulation of mTORC2 Signaling. Genes (Basel). 2020; 11(9). PMC: 7564249. DOI: 10.3390/genes11091045. View

15.

Krishna R, Mayer L . Multidrug resistance (MDR) in cancer. Mechanisms, reversal using modulators of MDR and the role of MDR modulators in influencing the pharmacokinetics of anticancer drugs. Eur J Pharm Sci. 2000; 11(4):265-83. DOI: 10.1016/s0928-0987(00)00114-7. View

16.

Peinado H, Olmeda D, Cano A . Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype?. Nat Rev Cancer. 2007; 7(6):415-28. DOI: 10.1038/nrc2131. View

17.

Wang Q, Zhang Y, Yang H . Pdcd4 knockdown up-regulates MAP4K1 expression and activation of AP-1 dependent transcription through c-Myc. Biochim Biophys Acta. 2012; 1823(10):1807-14. PMC: 3725281. DOI: 10.1016/j.bbamcr.2012.07.004. View

18.

Wedeken L, Ohnheiser J, Hirschi B, Wethkamp N, Klempnauer K . Association of Tumor Suppressor Protein Pdcd4 With Ribosomes Is Mediated by Protein-Protein and Protein-RNA Interactions. Genes Cancer. 2011; 1(3):293-301. PMC: 3092196. DOI: 10.1177/1947601910364227. View

19.

Wang Q, Zhang Y, Zhu J, Zheng H, Chen S, Chen L . IGF-1R inhibition induces MEK phosphorylation to promote survival in colon carcinomas. Signal Transduct Target Ther. 2020; 5(1):153. PMC: 7447751. DOI: 10.1038/s41392-020-0204-0. View

20.

Al-Malky H, Al Harthi S, Osman A . Major obstacles to doxorubicin therapy: Cardiotoxicity and drug resistance. J Oncol Pharm Pract. 2019; 26(2):434-444. DOI: 10.1177/1078155219877931. View