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Loss of TXNIP enhances peritoneal metastasis and can be abrogated by dual TORC1/2 inhibition


FOR IMMEDIATE RELEASE
2020-05-12

The cover for issue 86 of Oncotarget features Figure 6, "Schematic representation of the duality of TXNIP function as it pertains to peritoneal carcinomatosis/sarcomatosis," by Spaeth-Cook, et al.

Outliers were validated in The Cancer Genome Atlas and an ovarian tissue microarray and by modulation in ovarian cancer models in vitro and in peritoneal xenograft models.

Dr. James L. Chen from the Department of Biomedical Informatics, Division of Bioinformatics & the Department of Internal Medicine, Division of Medical Oncology, at The Ohio State University, in Columbus, OH 43210, USA said, "There is an unmet need to develop effective and novel treatment strategies to prevent and treat peritoneal metastasis (PM)"

"There is an unmet need to develop effective and novel treatment strategies to prevent and treat peritoneal metastasis (PM)"

- Dr. James L. Chen, Department of Biomedical Informatics, Division of Bioinformatics & the Department of Internal Medicine, Division of Medical Oncology, at The Ohio State University

Anoikis has been demonstrated to be an important mediator for acinar lumen formation in normal breast tissue, and anoikis resistance has been demonstrated to be critical for mammary tumor formation and metastases. Anoikis resistance is a hallmark of all cancer cells but may be especially important in the biology of PM as the primary mode of tumor dissemination.

Figure 6: Schematic representation of the duality of TXNIP function as it pertains to peritoneal carcinomatosis/sarcomatosis.

The research team and others have previously shown the importance of autophagy to the anoikis resistance phenotype in multiple spheroid cell line models derived from tumor types associated with PM. Conversely, a recent report on lung cancer patients demonstrated that TXNIP was hypoxia inducible in lung cancer cell lines and that patients with high levels of TXNIP had significantly shorter PFS which was maintained in a multivariate analysis.

In this paper, the research team identified TXNIP alterations and resultant TORC signaling changes as central to PM through the use of a novel clustering methodology that identifies outlier genes from gene expression data.

The James L. Chen research team concluded, "The effects of downregulated TXNIP on PM potentially can be overcome by the use of TORC1/2 inhibition."

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DOI - https://doi.org/10.18632/oncotarget.26281

Full text - https://www.oncotarget.com/article/26281/text/

Correspondence to - James L. Chen - James.Chen@osumc.edu

Keywords - carcinomatosis, sarcomatosis, TXNIP, peritoneal disease

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