Acta Scientific Cancer Biology (ASCB) (ISSN: 2582-4473)

Comprehensive Review Volume 5 Issue 9

Escalation of Efficacy and Prevention of Chemoresistance in Various Cancer Therapies by the Utilization of Targeting the Crosstalk Amongst MAPK/ERK Along with Hippo/MST Signaling - A Comprehensive Review

Kulvinder Kochar Kaur1*, Gautam Allahbadia2 and Mandeep Singh3

1Scientific Director, Dr Kulvinder Kaur Centre for Human Reproduction, Jalandhar, Punjab, India
2Scientific Director, Rotunda-A Centre for Human Reproduction, Mumbai, India
3Consultant Neurologist, Swami Satyan and Hospital, Jalandhar, Punjab, India

*Corresponding Author: Kulvinder Kochar Kaur, Scientific Director, Dr Kulvinder Kaur Centre for Human Reproduction, Jalandhar, Punjab, India.

Received: August 19, 2021; Published: August 31, 2021

Reprints View PDF Related Articles

Abstract

Earlier having reviewed the treatment of ovarian cancer, endometrial carcinoma, gestational trophoblastic disease ( GTD), along with colorectal cancer, breast cancer etc, here we decided to comprehensively evaluate the crosstalk of various signaling pathway implicated in cancer therapy, in particular how the crosstalk amongst mitogen activated protein kinase (MAPK )/extracellular signal -regulated kinase (ERK1/2) signaling pathway with the Hippo/MST signaling pathway knowledge might impact on the generation of newer therapies by getting insight into the harms of physiology of phosphatidyl inositide 3-kinase (PI3K)/activator of protein kinase B (AKT/mammalian target of rapamycin (mTOR) pathway and combining therapies targeting Hippo/MST signaling pathway might avoid in the generation of chemoresistance. In particular the ERK represents a part of the MAPK signaling pathway that is amarkedly conserved pathway of signal transduction. This MAPK gets constituted by three separate kinases, like RAF/MEK as well as ERK. Impairment of the MAPK signaling takes place in a lot of pathophysiological conditions that are inclusive of neurodegenerative diseases, (NGD), Metabolic Syndrome (MetS) in addition to lot of cancers. Targeted hampering of the unique kinases belonging to the MAPK signaling pathway with the utilization of certain synthetic agents might work out to be of significant advantage for the treatment of cancer. Interaction of the MAPK signaling pathway with other proteins in addition to signaling pathways possess a key influence on the Clinical results of targeted treatments, besides possessing a significant part at the time of generation of drug resistance In cancers. Here we have tried to detail the interaction of the MAPK signaling pathway with rest of the signaling pathways specifically its crosstalk with the Hippo/MST signaling pathway, besides detailing how it may prove advantageous on utilization of targeting of these particular pathways In combination in the generation of anticancer treatments that turn out to possess greater efficacy.

Keywords: MAPK; ERK; Hippo; MST; PI3K; YAP; Cancer; Caspases; Natural Agents; Apoptosis

References

  1. Burotto M., et al. “The MAPK pathway across different malignancies: a new perspective”. Cancer 22 (2014): 3446-3456.
  2. Chappell WH., et al. “Ras/Raf/MEK/ERKand with PI3K/ PTEN/AKT/ mTOR:rationale and imortanc of inhibiting these pathway in human health”. Oncotarget 2 (2011): 135-164.
  3. Oughtred R., et al. “The. BioGRID interaction databases: 2019 update”. Nucleic Acids Research 47 (2019): D529-D541.
  4. Valis K and Novak P. “Targeting ERK- Hippo interplay in cancer therapy”. International Journal of Molecular Sciences 21 (2020): 3236.
  5. Ramkisson A., et al. “Targeted inhibition of the dual specificity phosphatases DUSP1and DUSP6 suppress MPNST growth via JNK”. Clinical Cancer Research 25 (2019): 4117-4127.
  6. Jin T., et al. “PTPN7 promotes the progression of glioma by activating the MAPK/ERK and the PI3K/ AKT pathways and is associated with poor patient survival”. Oncology Report 42 (2019): 717-723.
  7. Stevens C., et al. “A germline mutation In the death domain of DAPK1 inactivates ERK induced apoptosis”. Journal of Biological Chemistry 282 (2007): 13791-13803.
  8. Lian YF., et al. “CACYPB enhances cytoplasmic reduction of P-27 (Kip1) to promote Hepatocellular carcinomaprogression in the absenc of RNF41 mediated degradation”. Theranostics 9 (2019): 8392-408.
  9. , et al. “Gosspol inhibits cullin neddylation by targeting SAG-CUL5 and RBX-CUL1 complexes”. Neoplasia 22 (2020): 179-191.
  10. , et al. “HMG-CoA reducatase and Insig 1, two polytopic endoplasmic reticulum proteins, en route to proteasomal degradation”. Molecular Biology of the Cell 20 (2009): 3330-3341.
  11. Gastelum G., et al. “Restoration of the prolyl - hydroxylase domain protein-3 oxygen sensing mechanism is responsible for regulation of HIF 2 alpha expression and induction of sensitivity of myeloma cells to Hypoxia –mediated apoptosis”. PLoS ONE 12 (2017): e188438.
  12. Hogel H., et al. “Prolyl hydroxylase PHD3 enhances the Hypoxic survival and G1 to S transition of, carcinoma cells”. PLoS ONE 6 (2011): e27112.
  13. Schoepflin ZR., et al. “PHD3 is a transcriptional coactivator of HIF 1 alpha in nucleus pulposus cells independent of the PKM2-JMJD5 axis”. FASEB Journal 31 (2017): 3831-3847.
  14. Hulea L., et al. “Translational and HIF 1 alpha dependent metabolic reprogramming underpin metabolic plasticity and responses to kinase inhibitors and biguanides”. Cell Metabolism 28 (2018): 817-832e8.
  15. Ding M., et al. “The mTOR targets 4E-BP1/2 Restrain tumor growth and promote Hypoxia tolerance in PTEN driven prostate cancer”. Molecular Cancer Research 16 (2018): 682-695.
  16. , et al. “YAP/TAZ at the roots of cancer”. Cancer Cell 29 (2016): 783-803.
  17. Arkun Y and Yasemi D. “Dynamics and control of ERK signaling pathway: sensitivity, biostability and oscillations”. PLoS ONE 13 (2018): e0195513.
  18. Wang J., et al. “A non canonical MEK/ERK signaling pathway regulates autophagy via regulating Beclin 1”. Journal of Biological Chemistry 183 (2009): 7388-7397.
  19. Roux PP., et al. “Tumor promotingphorbol esters and activated Ras inactivates the tuberous sclerosis tumor suppressor complex via p90 ribosomal S6 Kinase”. Proceedings of the National Academy of Sciences of the United States of America 101 (2004): 13489-13494.
  20. Ding Q., et al. “Erk associates with and primes GSK3beta for its inactivation resulting in up regulation of beta-catenin”. Molecular Cell 19 (2005): 159-170.
  21. Hornbeck PV., et al. “Phospho site: A bioinformatics resource dedicated to physiological proteins phosphorylation”. Proteomics 4 (2004): 1551-1561.
  22. Tsuiko O., et al. “A speculative outlook on embryonic aneuploidy: can molecular pathways be involved?” Developmental Biology 447 (2019): 3-13.
  23. Sheridan C., et al. “An ERK - dependent pathway to Noxa expression regulates apoptosis by platimum –based chemotherapeutic drugs”. Oncogene 29 (2010): 6428-6441.
  24. Elgendy M., et al. “Oncogenic Ras -induced expression of Noxa and Beclin -1promotes autophagic cell death and limits clonogenic survival”. Molecular Cell 42 (2011): 23-35.
  25. Xue H., et al. “The N-terminal tail coordinates with carbohydrate recognition domain to mediate galectin 3 induced apoptosis in Tcells”. Oncotarget 8 (2017): 49824-9838.
  26. Satoh R., et al. “Identification of ACA-28, a1’acetoxychavicol acetate analogue compound, as a novel modulator of ERK MAPK signaling which preferentially kills melanoma cells”. Gene Cells 8 (2017): 22-608-618.
  27. Pathania AS., et al. “The synthetic tryptanthrin analogue suppresses STAT3 signaling andinduces caspase dependent apoptosis via ERK upregulation In human leukaemia HL-60cells”. PLoS ONE 9 (2014): e110411.
  28. Zhang G., et al. “Beta thujaplicin induces autophagic cell death, apoptosis and cell cyclearrest through ROS mediated Akt and p38/ERK MAPK signaling in Hepatocellular carcinoma”. Cell Death and Disease 10 (2019): 255.
  29. Huang K., et al. “Honokiol induced apoptosis and induced autophagy via the ROS/ERK1/2 signaling pathway in human osteosarcoma cells in vitro and in vivo”. Cell Death and Disease 9 (2018): 157.
  30. Zhang P., et al. “w09, a novel autophagy enhancer, induces autophagy dependent cell apoptosis via activation of the EGFR mediated RAS-RAF1-MAP2K-MAPK1/3pathway”. Autophagy 13 (2017): 1093-1112.
  31. Valis K., et al. “Shikonin regulates C-MYC and GLUT1 expression through the MST1-YAP-1-TEADaxis”. Experimental Cell Research 349 (2016): 273-281.
  32. Valis K., et al. “Hippo/Mst1 stimulates transcription of the pro- apoptotic mediator NOXA in a FoxO1- dependent manner”. Cancer Research 71 (2011): 946-954.
  33. Ardestani A., et al. “MST1 is a key regulator of beta cell apoptosis and dysfunction in diabetes”. Nature Medicine 20 (2014): 385-397.
  34. Smoot RL., et al. “Platelet derived growth factor receptor regulates YAP-1 transcriptional activity via Src family kinase dependent tyrosine phosphorylation”. Journal of Cellular Biochemistry 119 (2018): 824-836.
  35. Collak EK., et al. “Threonine 120 phosphorylation regulated by phosphatidyl inositide 3-kinase/Akt and mammalian target of