{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T02:58:39Z","timestamp":1791687519832,"version":"4.3.4"},"reference-count":63,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T00:00:00Z","timestamp":1715126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Wisconsin Carbone Cancer Center (UWCCC) Breast DOT","award":["P30 CA014520"],"award-info":[{"award-number":["P30 CA014520"]}]},{"name":"University of Wisconsin Carbone Cancer Center (UWCCC) Breast DOT","award":["S10 OD023526"],"award-info":[{"award-number":["S10 OD023526"]}]},{"name":"NIH\/NCI","award":["P30 CA014520"],"award-info":[{"award-number":["P30 CA014520"]}]},{"name":"NIH\/NCI","award":["S10 OD023526"],"award-info":[{"award-number":["S10 OD023526"]}]},{"name":"Office of the Director\u2014NIH","award":["P30 CA014520"],"award-info":[{"award-number":["P30 CA014520"]}]},{"name":"Office of the Director\u2014NIH","award":["S10 OD023526"],"award-info":[{"award-number":["S10 OD023526"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Triple-negative breast cancer (TNBC) is characterized by the absence of the estrogen receptor, progesterone receptor, and receptor tyrosine kinase HER2 expression. Due to the limited number of FDA-approved targeted therapies for TNBC, there is an ongoing need to understand the molecular underpinnings of TNBC for the development of novel combinatorial treatment strategies. This study evaluated the role of the MerTK receptor tyrosine kinase on proliferation and invasion\/metastatic potential in TNBC. Immunohistochemical analysis demonstrated MerTK expression in 58% of patient-derived TNBC xenografts. The stable overexpression of MerTK in human TNBC cell lines induced an increase in proliferation rates, robust in vivo tumor growth, heightened migration\/invasion potential, and enhanced lung metastases. NanoString nCounter analysis of MerTK-overexpressing SUM102 cells (SUM102-MerTK) revealed upregulation of several signaling pathways, which ultimately drive cell cycle progression, reduce apoptosis, and enhance cell survival. Proteomic profiling indicated increased endoglin (ENG) production in SUM102-MerTK clones, suggesting that MerTK creates a conducive environment for increased proliferative and metastatic activity via elevated ENG expression. To determine ENG\u2019s role in increasing proliferation and\/or metastatic potential, we knocked out ENG in a SUM102-MerTK clone with CRISPR technology. Although this ENG knockout clone exhibited similar in vivo growth to the parental SUM102-MerTK clone, lung metastasis numbers were significantly decreased ~4-fold, indicating that MerTK enhances invasion and metastasis through ENG. Our data suggest that MerTK regulates a unique proliferative signature in TNBC, promoting robust tumor growth and increased metastatic potential through ENG upregulation. Targeting MerTK and ENG simultaneously may provide a novel therapeutic approach for TNBC patients.<\/jats:p>","DOI":"10.3390\/ijms25105109","type":"journal-article","created":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T12:27:11Z","timestamp":1715171231000},"page":"5109","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["MerTK Drives Proliferation and Metastatic Potential in Triple-Negative Breast Cancer"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7168-8680","authenticated-orcid":false,"given":"Mari","family":"Iida","sequence":"first","affiliation":[{"name":"Department of Human Oncology, University of Wisconsin-Madison, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8274-9104","authenticated-orcid":false,"given":"Bridget E.","family":"Crossman","sequence":"additional","affiliation":[{"name":"Department of Human Oncology, University of Wisconsin-Madison, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2289-5194","authenticated-orcid":false,"given":"Kourtney L.","family":"Kostecki","sequence":"additional","affiliation":[{"name":"Department of Human Oncology, University of Wisconsin-Madison, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine E.","family":"Glitchev","sequence":"additional","affiliation":[{"name":"Department of Human Oncology, University of Wisconsin-Madison, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlene A.","family":"Kranjac","sequence":"additional","affiliation":[{"name":"Department of Human Oncology, University of Wisconsin-Madison, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madisen T.","family":"Crow","sequence":"additional","affiliation":[{"name":"Department of Human Oncology, University of Wisconsin-Madison, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jillian M.","family":"Adams","sequence":"additional","affiliation":[{"name":"Department of Human Oncology, University of Wisconsin-Madison, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Liu","sequence":"additional","affiliation":[{"name":"Departments of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI 53726, USA"},{"name":"Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI 53792, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Ong","sequence":"additional","affiliation":[{"name":"Departments of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI 53726, USA"},{"name":"Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI 53792, USA"},{"name":"Department of Obstetrics and Gynecology, University of Wisconsin-Madison, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9488-1704","authenticated-orcid":false,"given":"David T.","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Experimental Therapeutics, Comprehensive Cancer Center, City of Hope, Duarte, CA 91010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9643-7626","authenticated-orcid":false,"given":"Ravi","family":"Salgia","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Experimental Therapeutics, Comprehensive Cancer Center, City of Hope, Duarte, CA 91010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deric L.","family":"Wheeler","sequence":"additional","affiliation":[{"name":"Department of Human Oncology, University of Wisconsin-Madison, Madison, WI 53705, USA"},{"name":"Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI 53792, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"524","DOI":"10.3322\/caac.21754","article-title":"Breast Cancer Statistics","volume":"72","author":"Giaquinto","year":"2022","journal-title":"CA A Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"100985","DOI":"10.1016\/j.eclinm.2021.100985","article-title":"Global Breast Cancer Incidence and Mortality Trends by Region, Age-Groups, and Fertility Patterns","volume":"38","author":"Lima","year":"2021","journal-title":"EClinicalMedicine"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"djv107","DOI":"10.1093\/jnci\/djv107","article-title":"Female Breast Cancer Incidence among Asian and Western Populations: More Similar than Expected","volume":"107","author":"Sung","year":"2015","journal-title":"JNCI J. Natl. Cancer Inst."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Almansour, N.M. (2022). Triple-Negative Breast Cancer: A Brief Review about Epidemiology, Risk Factors, Signaling Pathways, Treatment and Role of Artificial Intelligence. Front. Mol. Biosci., 9.","DOI":"10.3389\/fmolb.2022.836417"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/s41523-022-00468-0","article-title":"Triple Negative Breast Cancer: Pitfalls and Progress","volume":"8","author":"Zagami","year":"2022","journal-title":"NPJ Breast Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"731535","DOI":"10.3389\/fonc.2021.731535","article-title":"Targeted Therapeutic Strategies for Triple-Negative Breast Cancer","volume":"11","author":"Li","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Medina, M.A., Oza, G., Sharma, A., Arriaga, L.G., Hern\u00e1ndez, J.M.H., Rotello, V.M., and Ramirez, J.T. (2020). Triple-Negative Breast Cancer: A Review of Conventional and Advanced Therapeutic Strategies. Int. J. Environ. Res. Pu, 17.","DOI":"10.3390\/ijerph17062078"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1016\/j.cell.2010.06.011","article-title":"Cell Signaling by Receptor Tyrosine Kinases","volume":"141","author":"Lemmon","year":"2010","journal-title":"Cell"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Schlessinger, J. (2014). Receptor Tyrosine Kinases: Legacy of the First Two Decades. Cold Spring Harb. Perspect. Biol., 6.","DOI":"10.1101\/cshperspect.a008912"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/nrclinonc.2010.97","article-title":"Understanding Resistance to EGFR Inhibitors-Impact on Future Treatment Strategies","volume":"7","author":"Wheeler","year":"2010","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1200\/JOP.2017.023333","article-title":"Triple-Negative Breast Cancer: Current Practice and Future Directions","volume":"13","author":"Costa","year":"2017","journal-title":"J. Oncol. Pract."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1158\/1535-7163.MCT-13-1021","article-title":"Nuclear Epidermal Growth Factor Receptor Is a Functional Molecular Target in Triple-Negative Breast Cancer","volume":"13","author":"Brand","year":"2014","journal-title":"Mol. Cancer Ther."},{"key":"ref_13","first-page":"1609","article-title":"A Perspective on Anti-EGFR Therapies Targeting Triple-Negative Breast Cancer","volume":"6","author":"Nakai","year":"2016","journal-title":"Am. J. Cancer Res."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"L\u00f3pez-Mej\u00eda, J.A., Tallabs-Utrilla, L.F., Salazar-Sojo, P., Mantilla-Ollarves, J.C., S\u00e1nchez-Carballido, M.A., and Rocha-Zavaleta, L. (2022). C-Kit Induces Migration of Triple-Negative Breast Cancer Cells and Is a Promising Target for Tyrosine Kinase Inhibitor Treatment. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23158702"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Jansson, S., Bendahl, P.-O., Grabau, D.A., Falck, A.-K., Fern\u00f6, M., Aaltonen, K., and Ryd\u00e9n, L. (2014). The Three Receptor Tyrosine Kinases C-KIT, VEGFR2 and PDGFR\u03b1, Closely Spaced at 4q12, Show Increased Protein Expression in Triple-Negative Breast Cancer. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0102176"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"16042","DOI":"10.1038\/sigtrans.2016.42","article-title":"The Paradoxical Functions of EGFR during Breast Cancer Progression","volume":"2","author":"Ali","year":"2017","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"079","DOI":"10.4103\/0974-2727.163129","article-title":"Epidermal Growth Factor Receptor Expression in Triple Negative and Nontriple Negative Breast Carcinomas","volume":"7","author":"Changavi","year":"2015","journal-title":"J. Lab. Physicians"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S0065-230X(08)00002-X","article-title":"TAM Receptor Tyrosine Kinases: Biologic Functions, Signaling, and Potential Therapeutic Targeting in Human Cancer","volume":"100","author":"Linger","year":"2008","journal-title":"Adv. Cancer Res."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Lemke, G. (2013). Biology of the TAM Receptors. Cold Spring Harbor Perspect. Biol., 5.","DOI":"10.1101\/cshperspect.a009076"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1038\/nrc3847","article-title":"The TAM Family: Phosphatidylserine-Sensing Receptor Tyrosine Kinases Gone Awry in Cancer","volume":"14","author":"Graham","year":"2014","journal-title":"Nat. Rev. Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"107577","DOI":"10.1016\/j.pharmthera.2020.107577","article-title":"MERTK in Cancer Therapy: Targeting the Receptor Tyrosine Kinase in Tumor Cells and the Immune System","volume":"213","author":"Huelse","year":"2020","journal-title":"Pharmacol. Therapeut."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/bs.ircmb.2022.04.004","article-title":"Mertk: An Emerging Target in Cancer Biology and Immuno-Oncology","volume":"368","author":"Lahey","year":"2022","journal-title":"Int. Rev. Cell. Mol. Bio."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1517\/14728222.2010.515980","article-title":"Taking Aim at Mer and Axl Receptor Tyrosine Kinases as Novel Therapeutic Targets in Solid Tumors","volume":"14","author":"Linger","year":"2010","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3420","DOI":"10.1038\/onc.2012.355","article-title":"Mer or Axl Receptor Tyrosine Kinase Inhibition Promotes Apoptosis, Blocks Growth and Enhances Chemosensitivity of Human Non-Small Cell Lung Cancer","volume":"32","author":"Linger","year":"2012","journal-title":"Oncogene"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3618","DOI":"10.1074\/jbc.M706906200","article-title":"Autophosphorylation Docking Site Tyr-867 in Mer Receptor Tyrosine Kinase Allows for Dissociation of Multiple Signaling Pathways for Phagocytosis of Apoptotic Cells and down-Modulation of Lipopolysaccharide-Inducible NF-KappaB Transcriptional Activation","volume":"283","author":"Tibrewal","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2297","DOI":"10.1158\/1535-7163.MCT-17-1239","article-title":"MERTK Mediates Intrinsic and Adaptive Resistance to AXL-Targeting Agents","volume":"17","author":"McDaniel","year":"2018","journal-title":"Mol. Cancer Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1038\/onc.2012.104","article-title":"Mer Receptor Tyrosine Kinase Promotes Invasion and Survival in Glioblastoma Multiforme","volume":"32","author":"Wang","year":"2013","journal-title":"Oncogene"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2257","DOI":"10.1172\/JCI67816","article-title":"MERTK Receptor Tyrosine Kinase Is a Therapeutic Target in Melanoma","volume":"123","author":"Schlegel","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1007\/s40265-013-0091-6","article-title":"Relapsed Triple-Negative Breast Cancer: Challenges and Treatment Strategies","volume":"73","author":"Guarneri","year":"2013","journal-title":"Drugs"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4429","DOI":"10.1158\/1078-0432.CCR-06-3045","article-title":"Triple-Negative Breast Cancer: Clinical Features and Patterns of Recurrence","volume":"13","author":"Dent","year":"2007","journal-title":"Clin. Cancer Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e150517","DOI":"10.1172\/JCI150517","article-title":"MERTK Activation Drives Osimertinib Resistance in EGFR-Mutant Non-Small Cell Lung Cancer","volume":"132","author":"Yan","year":"2022","journal-title":"J. Clin. Investig."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Chen, C.-J., and Liu, Y.-P. (2021). MERTK Inhibition: Potential as a Treatment Strategy in EGFR Tyrosine Kinase Inhibitor-Resistant Non-Small Cell Lung Cancer. Pharm, 14.","DOI":"10.3390\/ph14020130"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1038\/s41418-020-00651-5","article-title":"KPNB1-Mediated Nuclear Translocation of PD-L1 Promotes Non-Small Cell Lung Cancer Cell Proliferation via the Gas6\/MerTK Signaling Pathway","volume":"28","author":"Du","year":"2021","journal-title":"Cell Death Differ"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2014","DOI":"10.1158\/1535-7163.MCT-15-0116","article-title":"Small Molecule Inhibition of MERTK Is Efficacious in Non-Small Cell Lung Cancer Models Independent of Driver Oncogene Status","volume":"14","author":"Cummings","year":"2015","journal-title":"Mol. Cancer Ther."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2669","DOI":"10.1158\/0008-5472.CAN-18-2614","article-title":"Pan-TAM Tyrosine Kinase Inhibitor BMS-777607 Enhances Anti-PD-1 MAb Efficacy in a Murine Model of Triple-Negative Breast Cancer","volume":"79","author":"Kasikara","year":"2019","journal-title":"Cancer Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1158\/0008-5472.CAN-20-2066","article-title":"Axl and Mertk Receptors Cooperate to Promote Breast Cancer Progression by Combined Oncogenic Signaling and Evasion of Host Antitumor Immunity","volume":"81","author":"Davra","year":"2021","journal-title":"Cancer Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e85630","DOI":"10.1172\/jci.insight.85630","article-title":"The MERTK\/FLT3 Inhibitor MRX-2843 Overcomes Resistance-Conferring FLT3 Mutations in Acute Myeloid Leukemia","volume":"1","author":"Minson","year":"2016","journal-title":"JCI Insight"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.3324\/haematol.2021.278369","article-title":"AXL\/MERTK Inhibitor ONO-7475 Potently Synergizes with Venetoclax and Overcomes Venetoclax Resistance to Kill FLT3-ITD Acute Myeloid Leukemia","volume":"107","author":"Post","year":"2021","journal-title":"Haematologica"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"32678","DOI":"10.18632\/oncotarget.8724","article-title":"MERTK as a Novel Therapeutic Target in Head and Neck Cancer","volume":"7","author":"Sanders","year":"2016","journal-title":"Oncotarget"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1599","DOI":"10.1182\/blood-2013-01-478156","article-title":"Mer Receptor Tyrosine Kinase Is a Therapeutic Target in Pre\u2013B-Cell Acute Lymphoblastic Leukemia","volume":"122","author":"Linger","year":"2013","journal-title":"Blood"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1093\/neuonc\/nox111","article-title":"MerTK as a Therapeutic Target in Glioblastoma","volume":"20","author":"Wu","year":"2017","journal-title":"Neuro Oncol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"R11","DOI":"10.1186\/bcr3095","article-title":"Molecular Profiling of Patient-Derived Breast Cancer Xenografts","volume":"14","author":"Reyal","year":"2012","journal-title":"Breast Cancer Res. BCR"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"8305","DOI":"10.1038\/ncomms9305","article-title":"Vertical Suppression of the EGFR Pathway Prevents Onset of Resistance in Colorectal Cancers","volume":"6","author":"Misale","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"6468","DOI":"10.1158\/1078-0432.CCR-17-0615","article-title":"A Population of Heterogeneous Breast Cancer Patient-Derived Xenografts Demonstrate Broad Activity of PARP Inhibitor in BRCA1\/2 Wild-Type Tumors","volume":"23","author":"Evans","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_45","first-page":"molcanther.0922.2016","article-title":"JQ1 Induces DNA Damage and Apoptosis, and Inhibits Tumor Growth in a Patient-Derived Xenograft Model of Cholangiocarcinoma","volume":"17","author":"Garcia","year":"2017","journal-title":"Mol. Cancer Ther."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4850","DOI":"10.1158\/0008-5472.CAN-16-0058","article-title":"Diverse, Biologically Relevant, and Targetable Gene Rearrangements in Triple-Negative Breast Cancer and Other Malignancies","volume":"76","author":"Shaver","year":"2016","journal-title":"Cancer Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"35","DOI":"10.3233\/BD-2010-0307","article-title":"Triple Negative Breast Cancer Cell Lines: One Tool in the Search for Better Treatment of Triple Negative Breast Cancer","volume":"32","author":"Chavez","year":"2010","journal-title":"Breast Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"25737","DOI":"10.1074\/jbc.M114.570838","article-title":"Overexpression of MERTK Receptor Tyrosine Kinase in Epithelial Cancer Cells Drives Efferocytosis in a Gain-of-Function Capacity*","volume":"289","author":"Nguyen","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"eabe6156","DOI":"10.1126\/scisignal.abe6156","article-title":"TSHZ2 Is an EGF-Regulated Tumor Suppressor That Binds to the Cytokinesis Regulator PRC1 and Inhibits Metastasis","volume":"14","author":"Uribe","year":"2021","journal-title":"Sci. Signal"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1002\/hep.29478","article-title":"A MicroRNA-7\/Growth Arrest Specific 6\/TYRO3 Axis Regulates the Growth and Invasiveness of Sorafenib-resistant Cells in Human Hepatocellular Carcinoma","volume":"67","author":"Kabir","year":"2018","journal-title":"Hepatology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1158\/1535-7163.MCT-09-0707","article-title":"Inhibition of Mer and Axl Receptor Tyrosine Kinases in Astrocytoma Cells Leads to Increased Apoptosis and Improved Chemosensitivity","volume":"9","author":"Keating","year":"2010","journal-title":"Mol. Cancer Ther."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2060","DOI":"10.1016\/j.jid.2020.01.031","article-title":"Inhibition of Endoglin Exerts Antitumor Effects through the Regulation of Non-Smad TGF-\u03b2 Signaling in Angiosarcoma","volume":"140","author":"Sakamoto","year":"2020","journal-title":"J. Investig Dermatol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"6331","DOI":"10.1158\/1078-0432.CCR-18-0329","article-title":"Endoglin Expression on Cancer-Associated Fibroblasts Regulates Invasion and Stimulates Colorectal Cancer Metastasis","volume":"24","author":"Paauwe","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s10456-008-9101-9","article-title":"Endoglin in Angiogenesis and Vascular Diseases","volume":"11","author":"Dijke","year":"2008","journal-title":"Angiogenesis"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Liu, Y., Paauwe, M., Nixon, A.B., and Hawinkels, L.J.A.C. (2020). Endoglin Targeting: Lessons Learned and Questions That Remain. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22010147"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Mu\u00f1oz, T.G., Amaral, A.T., Puerto-Camacho, P., Peinado, H., and de \u00c1lava, E. (2021). Endoglin in the Spotlight to Treat Cancer. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22063186"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2934","DOI":"10.1096\/fj.201700867RR","article-title":"Endoglin Interacts with VEGFR2 to Promote Angiogenesis","volume":"32","author":"Tian","year":"2018","journal-title":"FASEB J."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1001\/jamaoncol.2021.3547","article-title":"Efficacy and Safety of TRC105 Plus Pazopanib vs. Pazopanib Alone for Treatment of Patients with Advanced Angiosarcoma","volume":"8","author":"Jones","year":"2022","journal-title":"JAMA Oncol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3744","DOI":"10.1158\/1078-0432.CCR-22-2462","article-title":"Endoglin, a Novel Biomarker and Therapeutical Target to Prevent Malignant Peripheral Nerve Sheath Tumor Growth and Metastasis","volume":"29","author":"Giannatale","year":"2023","journal-title":"Clin. Cancer Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1089\/adt.2021.140","article-title":"Modifications to the Transwell Migration\/Invasion Assay Method that Eases Assay Performance and Improves the Accuracy","volume":"20","author":"Stoellinger","year":"2022","journal-title":"Assay Drug Dev. Technol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Iida, M., McDaniel, N.K., Kostecki, K.L., Welke, N.B., Kranjac, C.A., Liu, P., Longhurst, C., Bruce, J.Y., Hong, S., and Salgia, R. (2022). AXL Regulates Neuregulin1 Expression Leading to Cetuximab Resistance in Head and Neck Cancer. BMC Cancer, 22.","DOI":"10.1186\/s12885-022-09511-6"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"4349","DOI":"10.1158\/1078-0432.CCR-19-3142","article-title":"AXL Mediates Cetuximab and Radiation Resistance through Tyrosine 821 and the C-ABL Kinase Pathway in Head and Neck Cancer","volume":"26","author":"McDaniel","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1002\/hed.27340","article-title":"Dual Axl\/MerTK Inhibitor INCB081776 Creates a Proinflammatory Tumor Immune Microenvironment and Enhances Anti-PDL1 Efficacy in Head and Neck Cancer","volume":"45","author":"Kostecki","year":"2023","journal-title":"Head Neck"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/10\/5109\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:41:33Z","timestamp":1760107293000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/10\/5109"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,8]]},"references-count":63,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["ijms25105109"],"URL":"https:\/\/doi.org\/10.3390\/ijms25105109","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,8]]}}}