ArticleEndocrinology2018
Elucidating the Role of the Maternal Embryonic Leucine Zipper Kinase in Adrenocortical Carcinoma.
Article in Endocrinology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- ADRENOCORTICAL CARCINOMA: AN ORPHAN MALIGNANCY: FROM THE PATIENT TO THE BENCH AND BACK.Transactions of the American Clinical and Climatological Association · 2024Article
- Antileukemic properties of the kinase inhibitor OTSSP167 in T-cell acute lymphoblastic leukemia.Blood advances · 2023Article
- Update on Biology and Genomics of Adrenocortical Carcinomas: Rationale for Emerging Therapies.Endocrine reviews · 2022Article
- An update on adrenocortical cell lines of human origin.Endocrine · 2022Review
- Pan-cancer network disorders revealed by overall and local signaling entropy.Journal of molecular cell biology · 2021Article
- Mastermind Like Transcriptional Coactivator 3 (MAML3) Drives Neuroendocrine Tumor Progression.Molecular cancer research : MCR · 2021Article
- Update on in-vivo preclinical research models in adrenocortical carcinoma.Current opinion in endocrinology, diabetes, and obesity · 2020Review
- Review
- Leptomeningeal Metastasis from Adrenocortical Carcinoma: A Case Report.Journal of the Endocrine Society · 2020Article
- Inhibition of MELK produces potential anti-tumour effects in bladder cancer by inducing G1/S cell cycle arrest via the ATM/CHK2/p53 pathway.Journal of cellular and molecular medicine · 2020Article
- Targeting PDZ-binding kinase is anti-tumorigenic in novel preclinical models of ACC.Endocrine-related cancer · 2019Article
- Contemporary preclinical human models of adrenocortical carcinoma.Current opinion in endocrine and metabolic research · 2019Article
- DLK1/PREF1 marks a novel cell population in the human adrenal cortex.The Journal of steroid biochemistry and molecular biology · 2019Article
- Identification of important invasion and proliferation related genes in adrenocortical carcinoma.Medical oncology (Northwood, London, England) · 2019Article
- Targeted Assessment ofClinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- A Conditional Dependency on MELK for the Proliferation of Triple-Negative Breast Cancer Cells.iScience · 2018Article
- Therapeutic Targets for Adrenocortical Carcinoma in the Genomics Era.Journal of the Endocrine Society · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Adrenocortical carcinoma (ACC) is an aggressive cancer with a 5-year survival rate <35%. Mortality remains high due to lack of targeted therapies. Using bioinformatic analyses, we identified maternal embryonic leucine zipper kinase (MELK) as 4.1-fold overexpressed in ACC compared with normal adrenal samples. High MELK expression in human tumors correlated with shorter survival and with increased expression of genes involved in cell division and growth. We investigated the functional effects of MELK inhibition using newly developed ACC cell lines with variable MELK expression, CU-ACC1 and CU-ACC2, compared with H295R cells. In vitro treatment with the MELK inhibitor, OTSSP167, resulted in a dose-dependent decrease in rates of cell proliferation, colony formation, and cell survival, with relative sensitivity of each ACC cell line based upon the level of MELK overexpression. To confirm a MELK-specific antitumorigenic effect, MELK was inhibited in H295R cells via multiple short hairpin RNAs. MELK silencing resulted in 1.9-fold decrease in proliferation, and 3- to 10-fold decrease in colony formation in soft agar and clonogenicity assays, respectively. In addition, although MELK silencing had no effect on survival in normoxia, exposure to a hypoxia resulted in a sixfold and eightfold increase in apoptosis as assessed by caspase-3 activation and TUNEL, respectively. Together these data suggest that MELK is a modulator of tumor cell growth and survival in a hypoxic microenvironment in adrenal cancer cells and support future investigation of its role as a therapeutic kinase target in patients with ACC.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.