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Roles Each of Snail, Yin Yang 1, and RKIP in the Regulation of Tumor Cells Chemo- Immuno-Resistance to Apoptosis

Volume 4, Issue 1, 2013, pp. 79-92
DOI: 10.1615/ForumImmunDisTher.2013008299
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ABSTRACT

The current anti-cancer therapeutic armamentarium consists of surgery, chemotherapy, radiation, hormonal therapy, immunotherapy, and combinations thereof. Initial treatments usually result in objective clinical responses with prolongation of overall survival (OS) and progression-free survival (PFS) in a large subset of the treated patients. However, at the onset, a subset of patients does not respond, and another subset initially responds but experiences relapses and recurrences. These latter subsets of patients develop a state of crossresistance to a variety of unrelated therapies. Therefore, there is an urgent need to first unravel the underlying mechanisms of resistance and associated gene products that regulate the cross-resistance. Such gene products represent potential therapeutic targets as well as potential prognostic/diagnostic biomarkers. In this context, we have identified three interrelated gene products involved in resistance, namely, Snail, YY1, and RKIP that are components of the dysregulated NF-κB/Snail/YY1/RKIP loop in many cancers. In this review, we discuss the roles each of Snail, YY1, and RKIP in the regulation of tumor cell resistance to chemo- and immunotherapies. Because these gene products have also been shown to be involved in the regulation of the EMT phenotype and metastasis, we hypothesize that targeting any of these gene products can simultaneously inhibit tumor cell resistance and metastasis.

CITED BY
  1. Escara-Wilke June, Keller Jill M., Ignatoski Kathleen M. Woods, Dai Jinlu, Shelley Gregory, Mizokami Atsushi, Zhang Jian, Yeung Miranda L, Yeung Kam C., Keller Evan T., Raf kinase inhibitor protein (RKIP) deficiency decreases latency of tumorigenesis and increases metastasis in a murine genetic model of prostate cancer, The Prostate, 75, 3, 2015. Crossref

  2. Francart Marie-Emilie, Lambert Justine, Vanwynsberghe Aline M., Thompson Erik W., Bourcy Morgane, Polette Myriam, Gilles Christine, Epithelial-mesenchymal plasticity and circulating tumor cells: Travel companions to metastases, Developmental Dynamics, 247, 3, 2018. Crossref

  3. Pothoulakis Charalabos, Torre-Rojas Monica, Duran-Padilla Marco A., Gevorkian Jonathan, Zoras Odysseas, Chrysos Emmanuel, Chalkiadakis George, Baritaki Stavroula, CRHR2/Ucn2 signaling is a novel regulator of miR-7/YY1/Fas circuitry contributing to reversal of colorectal cancer cell resistance to Fas-mediated apoptosis, International Journal of Cancer, 142, 2, 2018. Crossref

  4. Shvartsur Anna, Givechian Kevin B., Garban Hermes, Bonavida Benjamin, Overexpression of RKIP and its cross-talk with several regulatory gene products in multiple myeloma, Journal of Experimental & Clinical Cancer Research, 36, 1, 2017. Crossref

  5. Zaravinos Apostolos, Bonavida Benjamin, Chatzaki Ekaterini, Baritaki Stavroula, RKIP: A Key Regulator in Tumor Metastasis Initiation and Resistance to Apoptosis: Therapeutic Targeting and Impact, Cancers, 10, 9, 2018. Crossref

  6. Liu Hongyi, Li Peng, Li Bing, Sun Peng, Zhang Jiajin, Wang Baishi, Jia Baoqing, RKIP promotes cisplatin-induced gastric cancer cell death through NF-κB/Snail pathway, Tumor Biology, 36, 3, 2015. Crossref

  7. Zaravinos Apostolos, Kanellou Peggy, Lambrou George Ι., Spandidos Demetrios A., Gene set enrichment analysis of the NF-κB/Snail/YY1/RKIP circuitry in multiple myeloma, Tumor Biology, 35, 5, 2014. Crossref

  8. Falzone Luca, Candido Saverio, Salemi Rossella, Basile Maria S., Scalisi Aurora, McCubrey James A., Torino Francesco, Signorelli Salvatore S., Montella Maurizio, Libra Massimo, Computational identification of microRNAs associated to both epithelial to mesenchymal transition and NGAL/MMP-9 pathways in bladder cancer, Oncotarget, 7, 45, 2016. Crossref

  9. Touboul Roni, Baritaki Stavroula, Zaravinos Apostolos, Bonavida Benjamin, RKIP Pleiotropic Activities in Cancer and Inflammatory Diseases: Role in Immunity, Cancers, 13, 24, 2021. Crossref

  10. Hu Chi-Tan, Mandal JayaPrakash, Wu Wen-Sheng, Regulation on tumor metastasis by Raf kinase inhibitory protein: New insight with reactive oxygen species signaling, Tzu Chi Medical Journal, 33, 4, 2021. Crossref

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