{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T15:21:25Z","timestamp":1782400885119,"version":"3.54.5"},"reference-count":76,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T00:00:00Z","timestamp":1665964800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Foggia"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>One of the most dangerous aspects of cancer cell biology is their ability to grow, spread and form metastases in the main vital organs. The identification of dysregulated markers that drive intracellular signalling involved in the malignant transformation of neoplastic cells and the understanding of the mechanisms that regulate these processes is undoubtedly a key objective for the development of new and more targeted therapies. RAF-kinase inhibitor protein (RKIP) is an endogenous tumour suppressor protein that affects tumour cell survival, proliferation, and metastasis. RKIP might serve as an early tumour biomarker since it exhibits significantly different expression levels in various cancer histologies and it is often lost during metastatic progression. In this review, we discuss the specific impact of transcriptional, post-transcriptional and post-translational regulation of expression and activation\/inhibition of RKIP and focus on those tumours for which experimental data on all these factors are available. In this way, we could select how these processes cooperate with RKIP expression in (1) Lung cancer; (2) Colon cancer, (3) Breast cancer; (4) myeloid neoplasm and Multiple Myeloma, (5) Melanoma and (6) clear cell Renal Cell Carcinoma. Furthermore, since RKIP seems to be a key marker of the development of several tumours and it may be assessed easily in various biological fluids, here we discuss the potential role of RKIP dosing in more accessible biological matrices other than tissues. Moreover, this objective may intercept the still unmet need to identify new and more accurate markers for the early diagnosis and prognosis of many tumours.<\/jats:p>","DOI":"10.3390\/cancers14205070","type":"journal-article","created":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T05:08:02Z","timestamp":1665983282000},"page":"5070","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Understanding Mechanisms of RKIP Regulation to Improve the Development of New Diagnostic Tools"],"prefix":"10.3390","volume":"14","author":[{"given":"Massimo","family":"Papale","sequence":"first","affiliation":[{"name":"Unit of Clinical Pathology, Department of Laboratory Diagnostics, University Hospital \u201cPoliclinico Foggia\u201d, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3495-2707","authenticated-orcid":false,"given":"Giuseppe Stefano","family":"Netti","sequence":"additional","affiliation":[{"name":"Unit of Clinical Pathology, Center for Molecular Medicine, Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy"},{"name":"Unit of Nephology, Dialysis and Transplantation, Advanced Research Center on Kidney Aging (A.R.K.A.), Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Stallone","sequence":"additional","affiliation":[{"name":"Unit of Nephology, Dialysis and Transplantation, Advanced Research Center on Kidney Aging (A.R.K.A.), Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4996-3938","authenticated-orcid":false,"given":"Elena","family":"Ranieri","sequence":"additional","affiliation":[{"name":"Unit of Clinical Pathology, Center for Molecular Medicine, Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy"},{"name":"Unit of Nephology, Dialysis and Transplantation, Advanced Research Center on Kidney Aging (A.R.K.A.), Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/sj.cr.7290105","article-title":"MAPK Signal Pathways in the Regulation of Cell Proliferation in Mammalian Cells","volume":"12","author":"Zhang","year":"2002","journal-title":"Cell Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1016\/j.bcp.2004.04.024","article-title":"The Role of Raf Kinase Inhibitor Protein (RKIP) in Health and Disease","volume":"68","author":"Keller","year":"2004","journal-title":"Biochem. Pharm."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cellsig.2007.07.003","article-title":"Signaling Crossroads: The Function of Raf Kinase Inhibitory Protein in Cancer, the Central Nervous System and Reproduction","volume":"20","author":"Klysik","year":"2008","journal-title":"Cell Signal"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1038\/nature02158","article-title":"Protein Kinase C Switches the Raf Kinase Inhibitor from Raf-1 to GRK-2","volume":"426","author":"Lorenz","year":"2003","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1615\/CritRevOncog.2014011950","article-title":"Interactions of RKIP with Inflammatory Signaling Pathways","volume":"19","author":"Zhao","year":"2014","journal-title":"Crit. Rev. Oncog."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"7207","DOI":"10.1128\/MCB.21.21.7207-7217.2001","article-title":"Raf Kinase Inhibitor Protein Interacts with NF-\u039aB-Inducing Kinase and TAK1 and Inhibits NF-\u039aB Activation","volume":"21","author":"Yeung","year":"2001","journal-title":"Mol. Cell Biol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Touboul, R., Baritaki, S., Zaravinos, A., and Bonavida, B. (2021). RKIP Pleiotropic Activities in Cancer and Inflammatory Diseases: Role in Immunity. Cancers, 13.","DOI":"10.3390\/cancers13246247"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Gabriela-Freitas, M., Pinheiro, J., Raquel-Cunha, A., Cardoso-Carneiro, D., and Martinho, O. (2019). RKIP as an Inflammatory and Immune System Modulator: Implications in Cancer. Biomolecules, 9.","DOI":"10.3390\/biom9120769"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1158\/0008-5472.CAN-10-3102","article-title":"Raf Kinase Inhibitor Protein RKIP Enhances Signaling by Glycogen Synthase Kinase-3\u03b2","volume":"71","author":"Bitar","year":"2011","journal-title":"Cancer Res."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Yesilkanal, A., and Rosner, M. (2018). Targeting Raf Kinase Inhibitory Protein Regulation and Function. Cancers, 10.","DOI":"10.3390\/cancers10090306"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1186\/1476-4598-13-193","article-title":"MiR-27a Regulates Cisplatin Resistance and Metastasis by Targeting RKIP in Human Lung Adenocarcinoma Cells","volume":"13","author":"Li","year":"2014","journal-title":"Mol. Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1136\/gut.2005.082859","article-title":"Extensive DNA Methylation in Normal Colorectal Mucosa in Hyperplastic Polyposis","volume":"55","author":"Minoo","year":"2006","journal-title":"Gut"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1097\/PAI.0000000000000323","article-title":"Reduced RKIP Expression Is Associated with Breast Neoplastic Progression and Is Correlated With Poor Outcomes and Aberrant Methylation in Breast Carcinoma","volume":"25","author":"Kim","year":"2017","journal-title":"Appl. Immunohistochem. Mol. Morphol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1866","DOI":"10.3892\/ol.2017.5617","article-title":"Promoter Methylation and Expression of Raf Kinase Inhibitory Protein in Esophageal Squamous Cell Carcinoma","volume":"13","author":"Wei","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Zaravinos, A., Bonavida, B., Chatzaki, E., and Baritaki, S. (2018). RKIP: A Key Regulator in Tumor Metastasis Initiation and Resistance to Apoptosis: Therapeutic Targeting and Impact. Cancers, 10.","DOI":"10.3390\/cancers10090287"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Zhang, B., Wang, O., Qin, J., Liu, S., Sun, S., Liu, H., Kuang, J., Jiang, G., and Zhang, W. (2013). Cis-Acting Elements and Trans-Acting Factors in the Transcriptional Regulation of Raf Kinase Inhibitory Protein Expression. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0083097"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/35094009","article-title":"The Development of Androgen-Independent Prostate Cancer","volume":"1","author":"Feldman","year":"2001","journal-title":"Nat. Rev. Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2243","DOI":"10.1038\/sj.onc.1210860","article-title":"Snail Is a Repressor of RKIP Transcription in Metastatic Prostate Cancer Cells","volume":"27","author":"Beach","year":"2008","journal-title":"Oncogene"},{"key":"ref_19","first-page":"E364","article-title":"Network of Mutually Repressive Metastasis Regulators Can Promote Cell Heterogeneity and Metastatic Transitions","volume":"111","author":"Lee","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.ydbio.2009.08.009","article-title":"Regulation of Gene Expression via the Core Promoter and the Basal Transcriptional Machinery","volume":"339","author":"Kadonaga","year":"2010","journal-title":"Dev. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1615\/CritRevOncog.2014012025","article-title":"Genetic and Epigenetic Control of RKIP Transcription","volume":"19","author":"Datar","year":"2014","journal-title":"Crit. Rev. Oncog."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4500","DOI":"10.1038\/emboj.2011.312","article-title":"Signalling Pathway for RKIP and Let-7 Regulates and Predicts Metastatic Breast Cancer","volume":"30","author":"Yun","year":"2011","journal-title":"EMBO J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1016\/j.febslet.2009.12.051","article-title":"RKIP Inhibits NF-\u039aB in Cancer Cells by Regulating Upstream Signaling Components of the I\u03baB Kinase Complex","volume":"584","author":"Tang","year":"2010","journal-title":"FEBS Lett."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/emboj.2008.294","article-title":"Raf Kinase Inhibitory Protein Suppresses a Metastasis Signalling Cascade Involving LIN28 and Let-7","volume":"28","author":"Yun","year":"2009","journal-title":"EMBO J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1038\/ncb1508","article-title":"A Wnt\u2013Axin2\u2013GSK3\u03b2 Cascade Regulates Snail1 Activity in Breast Cancer Cells","volume":"8","author":"Yook","year":"2006","journal-title":"Nat. Cell Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.niox.2010.10.001","article-title":"Dual Role of NO Donors in the Reversal of Tumor Cell Resistance and EMT: Downregulation of the NF-\u039aB\/Snail\/YY1\/RKIP Circuitry","volume":"24","author":"Bonavida","year":"2011","journal-title":"Nitric Oxide"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"6217","DOI":"10.1158\/0008-5472.CAN-12-0402","article-title":"Raf Kinase Inhibitor RKIP Inhibits MDA-9\/Syntenin-Mediated Metastasis in Melanoma","volume":"72","author":"Das","year":"2012","journal-title":"Cancer Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1159\/000464120","article-title":"MiR-543 Promotes Proliferation and Epithelial-Mesenchymal Transition in Prostate Cancer via Targeting RKIP","volume":"41","author":"Du","year":"2017","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"94358","DOI":"10.18632\/oncotarget.21719","article-title":"LncRNA XIST Acts as a Tumor Suppressor in Prostate Cancer through Sponging MiR-23a to Modulate RKIP Expression","volume":"8","author":"Du","year":"2017","journal-title":"Oncotarget"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.bbrc.2012.07.025","article-title":"MicroRNA-224 Targets RKIP to Control Cell Invasion and Expression of Metastasis Genes in Human Breast Cancer Cells","volume":"425","author":"Huang","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Cross-Knorr, S., Lu, S., Perez, K., Guevara, S., Brilliant, K., Pisano, C., Quesenberry, P.J., Resnick, M.B., and Chatterjee, D. (2013). RKIP Phosphorylation and STAT3 Activation Is Inhibited by Oxaliplatin and Camptothecin and Are Associated with Poor Prognosis in Stage II Colon Cancer Patients. BMC Cancer, 13.","DOI":"10.1186\/1471-2407-13-463"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"40412","DOI":"10.18632\/oncotarget.16341","article-title":"Urinary RKIP\/p-RKIP Is a Potential Diagnostic and Prognostic Marker of Clear Cell Renal Cell Carcinoma","volume":"8","author":"Papale","year":"2017","journal-title":"Oncotarget"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1007\/s00018-020-03455-5","article-title":"PEBP1\/RKIP Behavior: A Mirror of Actin-Membrane Organization","volume":"77","author":"Schoentgen","year":"2020","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Schoentgen, F. (2020). Insight on the Role of RKIP in Cancer through Key Protein Partners and Cellular Protrusions. Prognostic and Therapeutic Applications of RKIP in Cancer, Elsevier.","DOI":"10.1016\/B978-0-12-819612-0.00001-8"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"7585","DOI":"10.18632\/aging.103169","article-title":"PTX3 Modulates the Immunoflogosis in Tumor Microenvironment and Is a Prognostic Factor for Patients with Clear Cell Renal Cell Carcinoma","volume":"12","author":"Netti","year":"2020","journal-title":"Aging"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Rascio, F., Spadaccino, F., Rocchetti, M.T., Castellano, G., Stallone, G., Netti, G.S., and Ranieri, E. (2021). The Pathogenic Role of PI3K\/AKT Pathway in Cancer Onset and Drug Resistance: An Updated Review. Cancers, 13.","DOI":"10.3390\/cancers13163949"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"18400","DOI":"10.1038\/s41598-020-75376-z","article-title":"Modulation of Complement Activation by Pentraxin-3 in Prostate Cancer","volume":"10","author":"Stallone","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4230","DOI":"10.1158\/0008-5472.CAN-14-0369","article-title":"Pentraxin 3: A Novel Biomarker for Predicting Progression from Prostatic Inflammation to Prostate Cancer","volume":"74","author":"Stallone","year":"2014","journal-title":"Cancer Res."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Gigante, M., and Ranieri, E. (2020). Methods to Study Posttranslational Modification Patterns in Cytotoxic T-Cells and Cancer. Cytotoxic T-Cells. Methods in Molecular Biology, Humana.","DOI":"10.1007\/978-1-0716-1507-2"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"5","DOI":"10.3322\/caac.21254","article-title":"Cancer Statistics, 2015","volume":"65","author":"Siegel","year":"2015","journal-title":"CA Cancer J. Clin."},{"key":"ref_41","first-page":"25","article-title":"NSCLC: An Update of Driver Mutations, Their Role in Pathogenesis and Clinical Significance","volume":"98","author":"Black","year":"2015","journal-title":"Rhode Isl. Med. J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4377","DOI":"10.1007\/s13277-013-1575-4","article-title":"Clinical Significance of RKIP MRNA Expression in Non-Small Cell Lung Cancer","volume":"35","author":"Wang","year":"2014","journal-title":"Tumor Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3039","DOI":"10.3892\/ol.2017.5846","article-title":"Reduced RKIP Expression Levels Are Associated with Frequent Non-Small Cell Lung Cancer Metastasis and STAT3 Phosphorylation and Activation","volume":"13","author":"Wang","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3068","DOI":"10.1200\/JCO.2021.39.15_suppl.3068","article-title":"Association of Low RKIP Expression with Poor Prognosis in Non-Small Cell Lung Cancer","volume":"39","author":"Meng","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"5605","DOI":"10.2147\/OTT.S149200","article-title":"RKIP Reduction Enhances Radioresistance by Activating the Shh Signaling Pathway in Non-Small-Cell Lung Cancer","volume":"10","author":"Xie","year":"2017","journal-title":"Onco Targets Ther."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2018\/1687097","article-title":"Aberrant Expression of MiR-362 Promotes Lung Cancer Metastasis through Downregulation of Sema3A","volume":"2018","author":"Luo","year":"2018","journal-title":"J. Immunol. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1002\/cam4.2822","article-title":"LINC-PINT Alleviates Lung Cancer Progression via Sponging MiR-543 and Inducing PTEN","volume":"9","author":"Wang","year":"2020","journal-title":"Cancer Med."},{"key":"ref_48","first-page":"3985","article-title":"SFTA1P, LINC00968, GATA6-AS1, TBX5-AS1, and FEZF1-AS1 Are Crucial Long Non-coding RNAs Associated with the Prognosis of Lung Squamous Cell Carcinoma","volume":"18","author":"Xiong","year":"2019","journal-title":"Oncol. Lett."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"9327","DOI":"10.2147\/CMAR.S254184","article-title":"LncRNA GATA6-AS1 Inhibits the Progression of Non-Small Cell Lung Cancer via Repressing MicroRNA-543 to Up-Regulating RKIP","volume":"12","author":"Gong","year":"2020","journal-title":"Cancer Manag. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"39001","DOI":"10.1038\/srep39001","article-title":"MiR-150 Promotes Cellular Metastasis in Non-Small Cell Lung Cancer by Targeting FOXO4","volume":"6","author":"Li","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Raquel-Cunha, A., Cardoso-Carneiro, D., Reis, R.M., and Martinho, O. (2019). Current Status of Raf Kinase Inhibitor Protein (RKIP) in Lung Cancer: Behind RTK Signaling. Cells, 8.","DOI":"10.3390\/cells8050442"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Huerta-Yepez, S., Yoon, N.K., Hernandez-Cueto, A., Mah, V., Rivera-Pazos, C.M., Chatterjee, D., Vega, M.I., Maresh, E.L., Horvath, S., and Chia, D. (2011). Expression of Phosphorylated Raf Kinase Inhibitor Protein (PRKIP) Is a Predictor of Lung Cancer Survival. BMC Cancer, 11.","DOI":"10.1186\/1471-2407-11-259"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.lfs.2017.11.034","article-title":"Crosstalk between MAChRM3 and \u03922AR, via Acetylcholine PI3\/PKC\/PBEP1\/Raf-1 MEK1\/2\/ERK1\/2 Pathway Activation, in Human Bronchial Epithelial Cells after Long-Term Cigarette Smoke Exposure","volume":"192","author":"Albano","year":"2018","journal-title":"Life Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1309\/5D7MM22DAVGDT1R8","article-title":"Loss of Raf-1 Kinase Inhibitor Protein Expression Is Associated with Tumor Progression and Metastasis in Colorectal Cancer","volume":"127","author":"Minoo","year":"2007","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"5672","DOI":"10.1200\/JCO.2006.07.5499","article-title":"Raf Kinase Inhibitor Protein Expression in a Survival Analysis of Colorectal Cancer Patients","volume":"24","author":"Hagan","year":"2006","journal-title":"J. Clin. Oncol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s12929-015-0162-y","article-title":"Role of Raf-Kinase Inhibitor Protein in Colorectal Cancer and Its Regulation by Hydroxycamptothecine","volume":"22","author":"Nie","year":"2015","journal-title":"J. Biomed. Sci."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Oberg, A.L., French, A.J., Sarver, A.L., Subramanian, S., Morlan, B.W., Riska, S.M., Borralho, P.M., Cunningham, J.M., Boardman, L.A., and Wang, L. (2011). MiRNA Expression in Colon Polyps Provides Evidence for a Multihit Model of Colon Cancer. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0020465"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"7283","DOI":"10.1158\/1078-0432.CCR-11-1452","article-title":"Complex Patterns of Altered MicroRNA Expression during the Adenoma-Adenocarcinoma Sequence for Microsatellite-Stable Colorectal Cancer","volume":"17","author":"Bartley","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"444","DOI":"10.34172\/apb.2020.054","article-title":"MiR-330 Regulates Colorectal Cancer Oncogenesis by Targeting BACH1","volume":"10","author":"Shirjang","year":"2020","journal-title":"Adv. Pharm. Bull."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3091","DOI":"10.1158\/0008-5472.CAN-11-3546","article-title":"Polycomb Protein EZH2 Regulates Tumor Invasion via the Transcriptional Repression of the Metastasis Suppressor RKIP in Breast and Prostate Cancer","volume":"72","author":"Ren","year":"2012","journal-title":"Cancer Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.abb.2016.09.007","article-title":"RKIP Suppresses the Proliferation and Metastasis of Breast Cancer Cell Lines through Up-Regulation of MiR-185 Targeting HMGA2","volume":"610","author":"Zou","year":"2016","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_62","first-page":"446","article-title":"Clinical Implications for Loss or Diminution of Expression of Raf-1 Kinase Inhibitory Protein and Its Phosphorylated Form in Ductal Breast Cancer","volume":"3","author":"Bitar","year":"2013","journal-title":"Am. J. Cancer Res."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Zebisch, A., Caraffini, V., and Sill, H. (2019). RAF Kinase Inhibitor Protein in Myeloid Leukemogenesis. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20225756"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1182\/blood-2017-09-804906","article-title":"Loss of RKIP Is a Frequent Event in Myeloid Sarcoma and Promotes Leukemic Tissue Infiltration","volume":"131","author":"Caraffini","year":"2018","journal-title":"Blood"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3644","DOI":"10.1158\/0008-5472.CAN-15-3049","article-title":"Increased Expression of MiR-23a Mediates a Loss of Expression in the RAF Kinase Inhibitor Protein RKIP","volume":"76","author":"Hatzl","year":"2016","journal-title":"Cancer Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1615\/ForumImmunDisTher.v2.i2.90","article-title":"Unique Pattern of Overexpression of Raf-1 Kinase Inhibitory Protein in Its Inactivated Phosphorylated Form in Human Multiple Myeloma","volume":"2","author":"Baritaki","year":"2011","journal-title":"Immunopathol. Dis. Ther."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.3892\/ijo.2014.2511","article-title":"Overexpression of Yin Yang 1 in Bone Marrow-Derived Human Multiple Myeloma and Its Clinical Significance","volume":"45","author":"Liu","year":"2014","journal-title":"Int. J. Oncol."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Penas, C., Apraiz, A., Mu\u00f1oa, I., Arroyo-Berdugo, Y., Rasero, J., Ezkurra, P.A., Velasco, V., Subiran, N., Bosserhoff, A.K., and Alonso, S. (2020). RKIP Regulates Differentiation-Related Features in Melanocytic Cells. Cancers, 12.","DOI":"10.3390\/cancers12061451"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/j.acthis.2013.03.003","article-title":"Raf Kinase Inhibitor Protein (RKIP) and Phospho-RKIP Expression in Melanomas","volume":"115","author":"Cardile","year":"2013","journal-title":"Acta Histochem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1016\/j.ceb.2004.09.004","article-title":"Diverse Mechanisms Regulate Stem Cell Self-Renewal","volume":"16","author":"Molofsky","year":"2004","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"35","DOI":"10.3892\/ol.2013.1690","article-title":"NANOG Expression Correlates with Differentiation, Metastasis and Resistance to Preoperative Adjuvant Therapy in Oral Squamous Cell Carcinoma","volume":"7","author":"Watanabe","year":"2014","journal-title":"Oncol. Lett."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1016\/j.biocel.2013.02.017","article-title":"NANOG Promotes Liver Cancer Cell Invasion by Inducing Epithelial\u2013Mesenchymal Transition through NODAL\/SMAD3 Signaling Pathway","volume":"45","author":"Sun","year":"2013","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"7406","DOI":"10.18632\/oncotarget.1558","article-title":"Common Reduction of the Raf Kinase Inhibitory Protein in Clear Cell Renal Cell Carcinoma","volume":"5","author":"Hill","year":"2014","journal-title":"Oncotarget"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1038\/ki.1997.3","article-title":"Renal Cysts, Renal Cancer and von Hippel-Lindau Disease","volume":"51","author":"Neumann","year":"1997","journal-title":"Kidney Int."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1148\/radiol.2261011296","article-title":"Hereditary Renal Cancers","volume":"226","author":"Choyke","year":"2003","journal-title":"Radiology"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Bedri, S.K., Nilsson, O.B., Fink, K., M\u00e5nberg, A., Hamsten, C., Ayoglu, B., Manouchehrinia, A., Nilsson, P., Olsson, T., and Hillert, J. (2019). Plasma Protein Profiling Reveals Candidate Biomarkers for Multiple Sclerosis Treatment. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0217208"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/20\/5070\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:55:29Z","timestamp":1760144129000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/20\/5070"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,17]]},"references-count":76,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["cancers14205070"],"URL":"https:\/\/doi.org\/10.3390\/cancers14205070","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,17]]}}}