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

Nicholas W. Bateman, Pang Ning Teng, Erica Hope, Brian L. Hood, Julie Oliver, Wei Ao, Ming Zhou, Guisong Wang, Domenic Tommarello, Katlin Wilson, Tracy Litzy, Kelly A. Conrads, Chad A. Hamilton, Kathleen M. Darcy, Yovanni Casablanca, George Larry Maxwell, Victoria Bae-Jump, Thomas P. Conrads*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

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.

Original languageEnglish
Pages (from-to)1092-1103
Number of pages12
JournalCancer Medicine
Volume9
Issue number3
DOIs
StatePublished - 1 Feb 2020
Externally publishedYes

Keywords

  • HN1
  • JPT1
  • Jupiter microtubule-associated homolog 1
  • endometrial cancer
  • hematological and neurological expressed 1
  • metformin
  • proteomics

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