Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Small peptide inhibitor from the sequence of RUNX3 disrupts PAK1–RUNX3 interaction and abrogates its phosphorylation-dependent oncogenic function

Oncogene volume 40, pages 5327–5341 (2021)Cite this article

Subjects

Abstract

P21 Activated Kinase 1 (PAK1) is an oncogenic serine/threonine kinase known to play a significant role in the regulation of cytoskeleton and cell morphology. Runt-related transcription factor 3 (RUNX3) was initially known for its tumor suppressor function, but recent studies have reported the oncogenic role of RUNX3 in various cancers. Previous findings from our laboratory provided evidence that Threonine 209 phosphorylation of RUNX3 acts as a molecular switch in dictating the tissue-specific dualistic functions of RUNX3 for the first time. Based on these proofs and to explore the translational significance of these findings, we designed a small peptide (RMR) from the protein sequence of RUNX3 flanking the Threonine 209 phosphorylation site. The selection of this specific peptide from multiple possible peptides was based on their binding energies, hydrogen bonding, docking efficiency with the active site of PAK1 and their ability to displace PAK1–RUNX3 interaction in our prediction models. We found that this peptide is stable both in in vitro and in vivo conditions, not toxic to normal cells and inhibits the Threonine 209 phosphorylation in RUNX3 by PAK1. We also tested the efficacy of this peptide to block the RUNX3 Threonine 209 phosphorylation mediated tumorigenic functions in in vitro cell culture models, patient-derived explant (PDE) models and in in vivo tumor xenograft models. These results proved that this peptide has the potential to be developed as an efficient therapeutic molecule for targeting RUNX3 Threonine 209 phosphorylation-dependent tumor phenotypes.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Regulation of tumorigenic potential by phospho-RUNX3 at T209.
Fig. 2: In silico interaction studies for designing RUNX3 peptide.
Fig. 3: RMR peptide inhibits RUNX3 phosphorylation.
Fig. 4: PAK1 and peptide interaction assays.
Fig. 5: Analyzing the efficacy and cell uptake capability of BR2-RMR and RMR peptides.
Fig. 6: RMR peptide reduced the oncogenic potential of RUNX3.
Fig. 7: RMR peptide treatment reduced the migration capacity of cancer cells.
Fig. 8: Antitumor efficacy of RMR peptide in vivo.
Fig. 9: RMR peptide treatment reduced the proliferation of patient-derived explants (PDE).

Similar content being viewed by others

References

  1. Mevel R, Draper JE, Lie-A-Ling M, Kouskoff V, Lacaud G. RUNX transcription factors: orchestrators of development. Development. 2019;146:1–19.

    Article  CAS  Google Scholar 

  2. Kudo Y, Tsunematsu T, Takata T. Oncogenic role of RUNX3 in head and neck cancer. J Cell Biochem. 2011;112:387–93.

    Article  CAS  PubMed  Google Scholar 

  3. Woolf E, Xiao C, Fainaru O, Lotem J, Rosen D, Negreanu V, et al. Runx3 and Runx1 are required for CD8 T cell development during thymopoiesis. Proc Natl Acad Sci USA. 2003;100:7731–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Levanon D, Bettoun D, Harris-cerruti C, Woolf E, Negreanu V, Eilam R et al. The Runx3 transcription factor regulates development and survival of TrkC dorsal root ganglia neurons. Eur Mol Biol Organ. 2002;21. https://doi.org/10.1093/emboj/cdf370.

  5. Bledsoe KL, McGee-Lawrence ME, Camilleri ET, Wang X, Riester SM, van Wijnen AJ, et al. RUNX3 facilitates growth of Ewing sarcoma cells. Bone. 2008;23:1–7.

    Google Scholar 

  6. Chen F, Liu X, Bai J, Pei D, Zheng J. The emerging role of RUNX3 in cancer metastasis (Review). Oncol Rep. 2016;35:1227–36.

    Article  CAS  PubMed  Google Scholar 

  7. Chuang LSH, Ito Y. RUNX3 is multifunctional in carcinogenesis of multiple solid tumors. Oncogene. 2010;29:2605–15.

    Article  CAS  PubMed  Google Scholar 

  8. Selvarajan V, Osato M, Nah GSS, Yan J, Chung TH, Voon DCC, et al. RUNX3 is oncogenic in natural killer/T-cell lymphoma and is transcriptionally regulated by MYC. Leukemia. 2017;31:2219–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Lee CWL, Chuang LSH, Kimura S, Lai SK, Ong CW, Yan B, et al. RUNX3 functions as an oncogene in ovarian cancer. Gynecol Oncol. 2011;122:410–7.

    Article  CAS  PubMed  Google Scholar 

  10. Tsunematsu T, Kudo Y, Iizuka S, Ogawa I, Fujita T, Kurihara H et al. RUNX3 has an oncogenic role in head and neck cancer. PLoS ONE. 2009;4. https://doi.org/10.1371/journal.pone.0005892.

  11. Salto-Tellez M, Peh BK, Ito K, Tan SH, Chong PY, Han HC, et al. RUNX3 protein is overexpressed in human basal cell carcinomas. Oncogene. 2006;25:7646–9.

    Article  CAS  PubMed  Google Scholar 

  12. Damdinsuren A, Matsushita H, Ito M, Tanaka M, Jin G, Tsukamoto H, et al. FLT3-ITD drives Ara-C resistance in leukemic cells via the induction of RUNX3. Leuk Res. 2014;39:1405–13.

    Article  CAS  Google Scholar 

  13. Manandhar S, Lee YM. Emerging role of RUNX3 in the regulation of tumor microenvironment. BMB Rep. 2018;51:174–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Kumar A, Singhal M, Chopra C, Srinivasan S, Surabhi RP, Kanumuri R, et al. Threonine 209 phosphorylation on RUNX3 by Pak1 is a molecular switch for its dualistic functions. Oncogene. 2016:35:4857–65.

  15. Kumar A, Sundaram S, Rayala SK, Venkatraman G. UnPAKing RUNX3 functions–Both sides of the coin. Small GTPases. 2019;10:264–70.

    CAS  PubMed  Google Scholar 

  16. Radu M, Semenova G, Kosoff R, Chernoff J. PAK signalling during the development and progression of cancer. Nat Rev Cancer. 2014;14:13–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Alqaeisoom N, Qian C, Arachchige D, Colvin RA, Holub JM. Inhibiting phosphorylation of Tau (τ) proteins at Ser262 using peptide-based R1 domain mimetics. Int J Pept Res Ther. 2019;25:447–63.

    Article  CAS  Google Scholar 

  18. Moreira IS, Fernandes PA, Ramos MJ. Computational alanine scanning mutagenesis—an improved methodological approach. J Comput Chem. 2007;28:644–54.

    Article  CAS  PubMed  Google Scholar 

  19. Lim KJ, Sung BH, Shin JR, Lee YW, Kim DJ, Yang KS, et al. A cancer specific cell-penetrating peptide, BR2, for the efficient delivery of an scFv into cancer cells. PLoS ONE. 2013;8. https://doi.org/10.1371/journal.pone.0066084.

  20. Chi X-Z, Yang J-O, Lee K-Y, Ito K, Sakakura C, Li Q-L, et al. RUNX3 suppresses gastric epithelial cell growth by inducing p21WAF1/Cip1 expression in cooperation with transforming growth factor-activated SMAD. Mol Cell Biol. 2005;25:8097–107.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Yamamura Y, Wei LL, Inoue KI, Ida H, Ito Y. RUNX3 cooperates with FoxO3a to induce apoptosis in gastric cancer cells. J Biol Chem. 2006;281:5267–76.

    Article  CAS  PubMed  Google Scholar 

  22. Voon DCC, Wang H, Koo JKW, Nguyen TAP, Hor YT, Chu YS, et al. Runx3 protects gastric epithelial cells against epithelial-mesenchymal transition-induced cellular plasticity and tumorigenicity. Stem Cells. 2012;30:2088–99.

    Article  CAS  PubMed  Google Scholar 

  23. Tanaka S, Shiraha H, Nakanishi Y, Nishina SI, Matsubara M, Horiguchi S, et al. Runt-related transcription factor 3 reverses epithelial-mesenchymal transition in hepatocellular carcinoma. Int J Cancer. 2012;131:2537–46.

    Article  CAS  PubMed  Google Scholar 

  24. Lim J, Duong T, Do N, Do P, Kim J, et al. Antitumor activity of cell-permeable RUNX3 protein in gastric cancer cells. Bone. 2008;23:1–7.

    Google Scholar 

  25. Whittle MC, Izeradjene K, Rani PG, Feng L, Carlson MA, DelGiorno KE, et al. Thorsen and SRH. RUNX3 controls a metastatic switch in pancreatic ductal adenocarcinoma. Cell. 2016;25:289–313.

    Google Scholar 

  26. Date Y, Ito K. Oncogenic RUNX3: a link between p53 deficiency and MYC dysregulation. Mol Cells. 2020;43:176–81.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Goh YM, Cinghu S, Hong ETH, Lee YS, Kim JH, Jang JW, et al. Src kinase phosphorylates RUNX3 at tyrosine residues and localizes the protein in the cytoplasm. J Biol Chem. 2010;285:10122–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Eldar-Finkelman H, Eisenstein M. Peptide inhibitors targeting protein kinases. Curr Pharm Des. 2009;15:2463–70.

    Article  CAS  PubMed  Google Scholar 

  29. Thangaretnam KP, Gopisetty G, Ramanathan P, Rajkumar T. A polypeptide from the junction region sequence of EWS-FLI1 inhibits Ewing’s sarcoma cells, interacts with the EWS-FLI1 and partner proteins. Sci Rep. 2017;7:1–12.

    Article  CAS  Google Scholar 

  30. Otvos L, Wade JD. Current challenges in peptide-based drug discovery. Front Chem. 2014;2:8–11.

    Article  Google Scholar 

  31. Lee ACL, Harris JL, Khanna KK, Hong JH. A comprehensive review on current advances in peptide drug development and design. Int J Mol Sci. 2019;20:1–21.

    Google Scholar 

  32. Bird GH, Madani N, Perry AF, Princiotto AM, Supko JG, He X, et al. Hydrocarbon double-stapling remedies the proteolytic instability of a lengthy peptide therapeutic. Proc Natl Acad Sci USA. 2010;107:14093–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Powley IR, Patel M, Miles G, Pringle H, Howells L, Thomas A, et al. Patient-derived explants (PDEs) as a powerful preclinical platform for anti-cancer drug and biomarker discovery. Br J Cancer. 2020;122:735–44.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Raj GV, Sareddy GR, Ma S, Lee TK, Viswanadhapalli S, Li R, et al. Estrogen receptor coregulator binding modulators (ERXs) effectively target estrogen receptor positive human breast cancers. Elife 2017;6. https://doi.org/10.7554/eLife.26857.

  35. Bateman A. UniProt: a worldwide hub of protein knowledge. Nucleic Acids Res. 2019;47:D506–D515.

    Article  CAS  Google Scholar 

  36. Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ. Basic local alignment search tool. J Mol Biol. 1990;215:403–10.

    Article  CAS  PubMed  Google Scholar 

  37. Berman HM, Battistuz T, Bhat TN, Bluhm WF, Bourne PE, Burkhardt K, et al. The protein data bank. Acta Crystallogr D: Biol Crystallogr. 2002;58:899–907.

    Article  CAS  Google Scholar 

  38. Zhang Y. I-TASSER server for protein 3D structure prediction. BMC Bioinform. 2008;9:1–8.

    Article  CAS  Google Scholar 

  39. Jagadeeshan S, Subramanian A, Tentu S, Beesetti S, Singhal M, Raghavan S, et al. P21-activated kinase 1 (Pak1) signaling influences therapeutic outcome in pancreatic cancer. Ann Oncol. 2016;27:1546–56.

    Article  CAS  PubMed  Google Scholar 

  40. Kim DE, Chivian D, Baker D. Protein structure prediction and analysis using the Robetta server. Nucleic Acids Res. 2004;32:526–31.

    Article  CAS  Google Scholar 

  41. Shen Y, Maupetit J, Derreumaux P, Tufféry P. Improved PEP-FOLD approach for peptide and miniprotein structure prediction. J Chem Theory Comput. 2014;10:4745–58.

    Article  CAS  PubMed  Google Scholar 

  42. Thévenet P, Shen Y, Maupetit J, Guyon F, Derreumaux P, Tufféry P. PEP-FOLD: an updated de novo structure prediction server for both linear and disulfide bonded cyclic peptides. Nucleic Acids Res. 2012;40:288–93.

    Article  CAS  Google Scholar 

  43. van Zundert GCP, Rodrigues JPGLM, Trellet M, Schmitz C, Kastritis PL, Karaca E, et al. The HADDOCK2.2 web server: user-friendly integrative modeling of biomolecular complexes. J Mol Biol. 2016;428:720–5.

    Article  PubMed  CAS  Google Scholar 

  44. Beard H, Cholleti A, Pearlman D, Sherman W, Loving KA. Applying physics-based scoring to calculate free energies of binding for single amino acid mutations in protein-protein complexes. PLoS ONE. 2013;8:1–11.

    Article  CAS  Google Scholar 

  45. Hess B, Kutzner C, Van Der Spoel D, Lindahl E. GRGMACS 4: algorithms for highly efficient, load-balanced, and scalable molecular simulation. J Chem Theory Comput. 2008;4:435–47.

    Article  CAS  PubMed  Google Scholar 

  46. Raines RT. Fluorescence polarization assay to quantify protein-protein interactions: an update. Methods Mol Biol. 2015;1278:823–7.

  47. Soria G, Ben-Baruch A. The inflammatory chemokines CCL2 and CCL5 in breast cancer. Cancer Lett. 2008;267:271–85.

    Article  CAS  PubMed  Google Scholar 

  48. Gao L, Wang FQ, Li HM, Yang JG, Ren JG, He KF, et al. CCL2/EGF positive feedback loop between cancer cells and macrophages promotes cell migration and invasion in head and neck squamous cell carcinoma. Oncotarget. 2016;7:87037–51.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Sauter W, Rosenberger A, Beckmann L, Kropp S, Mittelstrass K, Timofeeva M, et al. Matrix metalloproteinase 1 (MMP1) is associated with early-onset lung cancer. Cancer Epidemiol Biomark Prev. 2008;17:1127–35.

    Article  CAS  Google Scholar 

  50. George A, Ranganathan K, Rao UK. Expression of MMP-1 in histopathological different grades of oral squamous cell carcinoma and in normal buccal mucosa—an immunohistochemical study. Cancer Biomark. 2010;7:275–83.

    Article  CAS  PubMed  Google Scholar 

  51. Mendes O, Kim HT, Stoica G. Expression of MMP2, MMP9 and MMP3 in breast cancer brain metastasis in a rat model. Clin Exp Metastasis. 2005;22:237–46.

    Article  CAS  PubMed  Google Scholar 

  52. Sabóia TM, Reis MF, Martins ÂMC, Romanos HF, Tannure PN, Granjeiro JM, et al. DLX1 and MMP3 contribute to oral clefts with and without positive family history of cancer. Arch Oral Biol. 2015;60:223–8.

    Article  PubMed  CAS  Google Scholar 

  53. Cao LQ, Wang YN, Liang M, Pan MZ. CALB1 enhances the interaction between p53 and MDM2, and inhibits the senescence of ovarian cancer cells. Mol Med Rep. 2019;19:5097–104.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Zagani R, El-Assaad W, Gamache I, Teodoro JG. Inhibition of adipose triglyceride lipase (ATGL) by the putative tumor suppressor G0S2 or a small molecule inhibitor attenuates the growth of cancer cells. Oncotarget. 2015;6:28282–95.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Coto-Llerena M, Ercan C, Kancherla V, Taha-Mehlitz S, Eppenberger-Castori S, Soysal SD, et al. High expression of FAP in colorectal cancer is associated with angiogenesis and immunoregulation processes. Front Oncol. 2020;10:1–12.

    Article  Google Scholar 

  56. Solano-Iturri JD, Beitia M, Errarte P, Calvete-Candenas J, Etxezarraga MC, Loizate A, et al. Altered expression of fibroblast activation protein-α (FAP) in colorectal adenoma-carcinoma sequence and in lymph node and liver metastases. Aging (Albany NY). 2020;12:10337–58.

    Article  CAS  Google Scholar 

  57. Aljohani AI, Joseph C, Kurozumi S, Mohammed OJ, Miligy IM, Green AR, et al. Myxovirus resistance 1 (MX1) is an independent predictor of poor outcome in invasive breast cancer. Breast Cancer Res Treat. 2020;181:541–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Takehara M, Sato Y, Kimura T, Noda K, Miyamoto H, Fujino Y, et al. Cancer-associated adipocytes promote pancreatic cancer progression through SAA1 expression. Cancer Sci. 2020;111:2883–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Sung HJ, Ahn JM, Yoon YH, Rhim TY, Park CS, Park JY, et al. Identification and validation of SAA as a potential lung cancer biomarker and its involvement in metastatic pathogenesis of lung cancer. J Proteome Res. 2011;10:1383–95.

    Article  CAS  PubMed  Google Scholar 

  60. Pan J, Tang Y, Liu S, Li L, Yu B, Lu Y, et al. LIMD1-AS1 suppressed non-small cell lung cancer progression through stabilizing LIMD1 mRNA via hnRNP U. Cancer Med. 2020;9:3829–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. He W, Liu Q, Wang L, Chen W, Li N, Cao X. TLR4 signaling promotes immune escape of human lung cancer cells by inducing immunosuppressive cytokines and apoptosis resistance. Mol Immunol. 2007;44:2850–9.

    Article  CAS  PubMed  Google Scholar 

  62. Cao L, Zhang W, Liu X, Yang P, Wang J, Hu K, et al. The prognostic significance of PDE7B in cytogenetically normal acute myeloid leukemia. Sci Rep. 2019;9:1–8.

    Article  Google Scholar 

  63. Deng W, Gu X, Lu Y, Gu C, Zheng Y, Zhang Z, et al. Down-modulation of TNFSF15 in ovarian cancer by VEGF and MCP-1 is a pre-requisite for tumor neovascularization. Angiogenesis. 2012;15:71–85.

    Article  CAS  PubMed  Google Scholar 

  64. Zhang X, Xiao Z, Liu X, Du L, Wang L, Wang S, et al. The potential role of orm2 in the development of colorectal cancer. PLoS ONE. 2012;7:1–7.

    CAS  Google Scholar 

  65. Jiang Z, Xu Y, Cai S. CXCL10 expression and prognostic significance in stage II and III colorectal cancer. Mol Biol Rep. 2010;37:3029–36.

    Article  CAS  PubMed  Google Scholar 

  66. Douchi D, Ohtsuka H, Ariake K, Masuda K, Kawasaki S, Kawaguchi K, et al. Silencing of LRRFIP1 reverses the epithelial-mesenchymal transition via inhibition of the Wnt/β-catenin signaling pathway. Cancer Lett. 2015;365:132–40.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank Dr. Sanjay kumar and Franklin, Department of Biotechnology, Christian Medical College, Vellore, India for helping in peptide uptake studies using animal imaging. We thank Dr. Vidhyarani Shyamsunder, Balaji Dental College, India for the help in establishing Head & Neck PDE model. We thank Bamdeb Patra, Khwajah Mohinudeen, Dr. Ram Prasad, and Srikanth Swamy Swaroop, Indian Institute of Technology-Madras, India for helping in Flow-cytometry experiments, Mass spectrometry experiment, Serum stability assay and for protein expression study, respectively. We thank Dr. Yogesh and Anand, Centre for Toxicology and Developmental Research (CEFT), Sri Ramachandra Institute of Higher Education and Research, India for animal studies. We thank DAE-BRNS (35/14/41/2014-BRNS/2045), DBT (BT/PR14340/NNT/28/860/2015) Government of India for financial support to SKR and the Department of Biotechnology, Indian Institute of Technology Madras (IITM) for infrastructural facilities. JJ thank the DST-INDO TAIWAN (GITA/DST/TWN/P-86/2019 dated: 04.03.2020), Board of Research in Nuclear Sciences (BRNS) (35/14/ 02/2018 BRNS/35009), DST-Fund for Improvement of S&T Infrastructure in Universities & Higher Educational Institutions (FIST) (SR/FST/LSI-667/2016) (C), DST-Promotion of University Research and Scientific Excellence (PURSE) (No. SR/PURSE Phase 2/38 (G), 2017 and JB is grateful to the UGC OBC National Fellowship (F./2015-16/NFO-2015-17-OBC-PON-29027).

Author information

Author notes

  1. Aruna Kumar Chelluboyina

    Present address: Division of General Medical Sciences – Oncology, Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA

  2. These authors contributed equally: Rahul Kanumuri, Aruna Kumar Chelluboyina.

Authors and Affiliations

  1. Department of Biotechnology, Indian Institute of technology Madras (IITM), Chennai, Tamilnadu, India

    Rahul Kanumuri, Aruna Kumar Chelluboyina, Ravichandran Vignesh, Gopala Krishna Aradhyam & Suresh K. Rayala

  2. Department of Human Genetics, Sri Ramachandra Faculty of Biomedical Sciences & Technology, Sri Ramachandra Institute of Higher Education & Research (Deemed to be University), Porur, Chennai, Tamilnadu, India

    Rahul Kanumuri, Akkanapally Venu, B. Vaishnavi & Ganesh Venkatraman

  3. Structural Biology and Bio-Computing Lab, Department of Bioinformatics, Science Block, Alagappa University, Karaikudi, India

    Jayashree Biswal & Jeyakanthan Jeyaraman

  4. Unit of Excellence in Cancer Genetics, Department of Genetics, Centre for Excellence in Genomic Sciences, School of Biological Sciences, Madurai Kamaraj University, Madurai, India

    Jaishree Pandian & Kumaresan Ganesan

  5. Department of Pathology, Sri Ramachandra Institute of Higher Education & Research (Deemed to be University), Porur, Chennai, Tamilnadu, India

    DJ. Leena

Authors
  1. Rahul Kanumuri
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Aruna Kumar Chelluboyina
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jayashree Biswal
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ravichandran Vignesh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jaishree Pandian
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Akkanapally Venu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. B. Vaishnavi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. DJ. Leena
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jeyakanthan Jeyaraman
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Kumaresan Ganesan
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Gopala Krishna Aradhyam
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Ganesh Venkatraman
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Suresh K. Rayala
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

R.K., A.K. performed experiments; J.B., J.J. performed in silico studies; R.V., G.K.A. helped with in vitro interaction study; J.P., K.G. helped with microarray experiment and analysis; A.V., B.V. helped with tumor regression study; D.J.L. scored IHC slides; G.V. & S.K.R. conceived the idea, designed the work and analyzed the data. R.K., G.V. & S.K.R. wrote the paper.

Corresponding authors

Correspondence to Ganesh Venkatraman or Suresh K. Rayala.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kanumuri, R., Chelluboyina, A.K., Biswal, J. et al. Small peptide inhibitor from the sequence of RUNX3 disrupts PAK1–RUNX3 interaction and abrogates its phosphorylation-dependent oncogenic function. Oncogene 40, 5327–5341 (2021). https://doi.org/10.1038/s41388-021-01927-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41388-021-01927-x

This article is cited by

Search

Advanced search

Quick links