{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T19:05:03Z","timestamp":1792695903566,"version":"4.5.0"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T00:00:00Z","timestamp":1710979200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Among women, breast carcinoma is one of the most complex cancers, with one of the highest death rates worldwide. There have been significant improvements in treatment methods, but its early detection still remains an issue to be resolved. This study explores the multifaceted function of hyaluronan-mediated motility receptor (HMMR) in breast cancer progression. HMMR\u2019s association with key cell cycle regulators (AURKA, TPX2, and CDK1) underscores its pivotal role in cancer initiation and advancement. HMMR\u2019s involvement in microtubule assembly and cellular interactions, both extracellularly and intracellularly, provides critical insights into its contribution to cancer cell processes. Elevated HMMR expression triggered by inflammatory signals correlates with unfavorable prognosis in breast cancer and various other malignancies. Therefore, recognizing HMMR as a promising therapeutic target, the study validates the overexpression of HMMR in breast cancer and various pan cancers and its correlation with certain proteins such as AURKA, TPX2, and CDK1 through online databases. Furthermore, the pathways associated with HMMR were explored using pathway enrichment analysis, such as Gene Ontology, offering a foundation for the development of effective strategies in breast cancer treatment. The study further highlights compounds capable of inhibiting certain pathways, which, in turn, would inhibit the upregulation of HMMR in breast cancer. The results were further validated via MD simulations in addition to molecular docking to explore protein\u2013protein\/ligand interaction. Consequently, these findings imply that HMMR could play a pivotal role as a crucial oncogenic regulator, highlighting its potential as a promising target for the therapeutic intervention of breast carcinoma.<\/jats:p>","DOI":"10.3389\/fphar.2024.1361424","type":"journal-article","created":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T04:59:51Z","timestamp":1710997191000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Exploring HMMR as a therapeutic frontier in breast cancer treatment, its interaction with various cell cycle genes, and targeting its overexpression through specific inhibitors"],"prefix":"10.3389","volume":"15","author":[{"given":"Aisha","family":"Shabir","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hina","family":"Qayoom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burhan Ul","family":"Haq","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adel","family":"Abo Mansoor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adil","family":"Abdelrahim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irshad","family":"Ahmad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah","family":"Almilabairy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuzail","family":"Ahmad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manzoor Ahmad","family":"Mir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,3,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1002\/path.941","article-title":"The pattern of expression of the microtubule\u2010binding protein RHAMM\/IHABP in mammary carcinoma suggests a role in the invasive behaviour of tumour cells","volume":"195","author":"Assmann","year":"2001","journal-title":"J. pathology"},{"key":"B2","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1111\/wrr.12214","article-title":"Hyaluronan in wound healing: rediscovering a major player","volume":"22","author":"Aya","year":"2014","journal-title":"Wound repair Regen."},{"key":"B3","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1016\/s1097-2765(03)00392-7","article-title":"Structural basis of Aurora-A activation by TPX2 at the mitotic spindle","volume":"12","author":"Bayliss","year":"2003","journal-title":"Mol. cell"},{"key":"B4","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1016\/j.neo.2017.05.002","article-title":"UALCAN: a portal for facilitating tumor subgroup gene expression and survival analyses","volume":"19","author":"Chandrashekar","year":"2017","journal-title":"Neoplasia"},{"key":"B5","doi-asserted-by":"publisher","first-page":"2248","DOI":"10.4161\/cc.29270","article-title":"Spatial regulation of Aurora A activity during mitotic spindle assembly requires RHAMM to correctly localize TPX2","volume":"13","author":"Chen","year":"2014","journal-title":"Cell cycle"},{"key":"B6","doi-asserted-by":"publisher","first-page":"20941","DOI":"10.18632\/oncotarget.24939","article-title":"Immunohistochemical analysis of RHAMM expression in normal and neoplastic human tissues: a cell cycle protein with distinctive expression in mitotic cells and testicular germ cells","volume":"9","author":"Chen","year":"2018","journal-title":"Oncotarget"},{"key":"B7","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1080\/15384101.2020.1728014","article-title":"Mitotic kinase anchoring proteins: the navigators of cell division","volume":"19","author":"Fulcher","year":"2020","journal-title":"Cell cycle"},{"key":"B8","doi-asserted-by":"publisher","first-page":"jcs232314","DOI":"10.1242\/jcs.232314","article-title":"Phosphorylation of importin-\u03b11 by CDK1\u2013cyclin B1 controls mitotic spindle assembly","volume":"132","author":"Guo","year":"2019","journal-title":"J. cell Sci."},{"key":"B9","doi-asserted-by":"publisher","first-page":"956","DOI":"10.1593\/neo.09694","article-title":"RHAMM (CD168) is overexpressed at the protein level and may constitute an immunogenic antigen in advanced prostate cancer disease","volume":"11","author":"Gust","year":"2009","journal-title":"Neoplasia"},{"key":"B10","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1002\/(SICI)1098-1004(200001)15:1<57::AID-HUMU12>3.0.CO;2-G","article-title":"Online Mendelian inheritance in man (OMIM)","volume":"15","author":"Hamosh","year":"2000","journal-title":"Hum. 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