Cancer medicine (Malden, MA), 2020-02, Vol.9 (3), p.1092-1103
2020
Details
- Autor(en) / Beteiligte
- Titel
- Jupiter microtubule‐associated homolog 1 (JPT1): A predictive and pharmacodynamic biomarker of metformin response in endometrial cancers
- Ist Teil von
- Cancer medicine (Malden, MA), 2020-02, Vol.9 (3), p.1092-1103
- Ort / Verlag
- United States: John Wiley & Sons, Inc
- Erscheinungsjahr
- 2020
- Link zum Volltext
- Quelle
- Wiley Online Library - AutoHoldings Journals
- Beschreibungen/Notizen
- Preoperative use of metformin in obese women with endometrioid endometrial cancer (EEC) reduces tumor proliferation and inhibits the mammalian target of rapamycin pathway, though is only effective in select cases. This study sought to identify a predictive and/or pharmacodynamic proteomic signature of metformin response to tailor its pharmacologic use. Matched pre‐ and post‐metformin‐treated tumor tissues from a recently completed preoperative window trial of metformin in EEC patients (ClinicalTrials.gov: NCT01911247) were analyzed by mass spectrometry (MS)‐based proteomic and immunohistochemical analyses. Jupiter microtubule‐associated homolog 1 (JPT1) was significantly elevated in metformin responders (n = 13) vs nonresponders (n = 7), and found to decrease in abundance in metformin responders following treatment; observations that were verified by immunohistochemical staining for JPT1. Metformin response and loss of JPT1 were assessed in RL95‐2 and ACI‐181 endometrial cancer (EC) cell lines. We further identified that silencing of JPT1 abundance does not alter cellular response to metformin or basal cell proliferation, but that JPT1 abundance does decrease in response to metformin treatment in RL95‐2 and ACI‐181 EC cell lines. These data suggest that JPT1 represents a predictive and pharmacodynamic biomarker of metformin response that, if validated in larger patient populations, may enable preoperative EEC patient stratification to metformin treatment and the ability to monitor patient response. We report JPT1 (Jupiter microtubule‐associated homolog 1) as a predictive and pharmacodynamic biomarker candidate of metformin response in endometrial cancers.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2045-7634eISSN: 2045-7634DOI: 10.1002/cam4.2729Titel-ID: cdi_doaj_primary_oai_doaj_org_article_175e0bc27b9348a3a49bceb4ddbd3c53
- Format
- –
- Schlagworte
- Adolescent, Adult, Aged, Antidiabetics, Biomarkers, Biomarkers, Tumor - metabolism, Cancer Biology, Carcinoma, Endometrioid - complications, Carcinoma, Endometrioid - metabolism, Carcinoma, Endometrioid - pathology, Carcinoma, Endometrioid - therapy, Cell Cycle Proteins - genetics, Cell Cycle Proteins - metabolism, Cell growth, Cell Line, Tumor, Cell proliferation, Cell Proliferation - drug effects, Chemotherapy, Adjuvant - methods, Clinical Trials, Phase I as Topic, Drug Resistance, Neoplasm, Endometrial cancer, Endometrial Neoplasms - complications, Endometrial Neoplasms - metabolism, Endometrial Neoplasms - pathology, Endometrial Neoplasms - therapy, Endometrium, Endometrium - pathology, Endometrium - surgery, Female, Gene Knockdown Techniques, hematological and neurological expressed 1, HN1, Humans, Hysterectomy, JPT1, Jupiter microtubule-associated homolog 1, Kinases, Mass spectroscopy, Metformin, Metformin - pharmacology, Metformin - therapeutic use, Microtubule-Associated Proteins - genetics, Microtubule-Associated Proteins - metabolism, Middle Aged, Neoadjuvant Therapy - methods, Obesity - complications, Obesity - metabolism, Original Research, Pharmacodynamics, Proteomics, Rapamycin, Signal Transduction - drug effects, TOR protein, TOR Serine-Threonine Kinases - metabolism, Tumor cell lines, Womens health, Young Adult