Single-cell RNA sequencing comparison of the human metastatic prostate spine tumor microenvironment.

Spinal column tumors can be difficult to process for single-cell omic studies, given the heterogeneity in tissue. Here, we present a protocol for operating room-to-benchtop single-cell processing of clinical specimens from a prostate cancer patient. We describe steps for sample homogenization, red blood cell lysis, cryopreservation, and single-cell sequencing analysis. This protocol can be used to identify prognostic markers and therapeutic targets for patients with osseous spine metastases and better inform eligibility for clinical trials.

UDP-6-glucose dehydrogenase in hormonally responsive breast cancers.

Survival for metastatic breast cancer is low and thus, continued efforts to treat and prevent metastatic progression are critical. Estrogen is shown to promote aggressive phenotypes in multiple cancer models irrespective of estrogen receptor (ER) status. Similarly, UDP-Glucose 6-dehydrogenase (UGDH) a ubiquitously expressed enzyme involved in extracellular matrix precursors, as well as hormone processing increases migratory and invasive properties in cancer models. While the role of UGDH in cellular migration is defined, how it intersects with and impacts hormone signaling pathways associated with tumor progression in metastatic breast cancer has not been explored. Here we demonstrate that UGDH knockdown blunts estrogen-induced tumorigenic phenotypes (migration and colony formation) in ER+ and ER- breast cancer in vitro. Knockdown of UGDH also inhibits extravasation of ER- breast cancer ex vivo, primary tumor growth and animal survival in vivo in both ER+ and ER- breast cancer. We also use single cell RNA-sequencing to demonstrate that our findings translate to a human breast cancer clinical specimen. Our findings support the role of estrogen and UGDH in breast cancer progression provide a foundation for future studies to evaluate the role of UGDH in therapeutic resistance to improve outcomes and survival for breast cancer patients.

UDP-glucose dehydrogenase (UGDH) in clinical oncology and cancer biology.

UDP-glucose-6-dehydrogenase (UGDH) is a cytosolic, hexameric enzyme that converts UDP-glucose to UDP-glucuronic acid (UDP-GlcUA), a key reaction in hormone and xenobiotic metabolism and in the production of extracellular matrix precursors. In this review, we classify UGDH as a molecular indicator of tumor progression in multiple cancer types, describe its involvement in key canonical cancer signaling pathways, and identify methods to inhibit UGDH, its substrates, and its downstream products. As such, we position UGDH as an enzyme to be exploited as a potential prognostication marker in oncology and a therapeutic target in cancer biology.