Jupiter microtubule‐associated homolog 1 (JPT1): A predictive and pharmacodynamic biomarker of metformin response in endometrial cancers

Abstract

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. K E Y W O R D Sendometrial cancer, hematological and neurological expressed 1, HN1, JPT1, Jupiter microtubuleassociated homolog 1, metformin, proteomics | 1093 BATEMAN ET Al.

Complete pathological response following levonorgestrel intrauterine device in clinically stage 1 endometrial adenocarcinoma: Results of a randomized clinical trial

“…Epidemiological evidence suggested it is associated with improved survival in women diagnosed with EAC [23][24][25]. Ongoing trials will determine the effectiveness of metformin in window of opportunity studies in EAC [26][27][28].…”

Circular RNA LPAR3 targets JPT1 via microRNA-513b-5p to facilitate glycolytic activation but repress prostate cancer radiosensitivity

“…Next, it was further figured out the downstream target genes of miR-513-5p. JPT1 is a protein-coding gene that impacts cell apoptosis and signal transduction (Bateman et al, 2020). A previous study has clarified that JPT1 is linked with the progression of PCa (Cheng et al, 2021).…”

PPP1R14B is a diagnostic prognostic marker in patients with uterine corpus endometrial carcinoma

“…In addition, among the genes closely associated with PPP1R14B expression, UBE2S, JPT1, and PTTG1 were associated with abnormal expression of endometrial cancer desiccations, proliferation, migration, methylation, and prediction of response to metformin therapy. [47][48][49][50] Our study suggested that the high expression of PPP1R14B may be related to gene mutation and tumour proliferation, invasion, and metastasis in UCEC patients.…”