The Cytoskeleton Effectors Rho-Kinase (ROCK) and Mammalian Diaphanous-Related (mDia) Formin Have Dynamic Roles in Tumor Microtube Formation in Invasive Glioblastoma Cells.

Glioblastoma (GBM) is a progressive and lethal brain cancer. Malignant control of actin and microtubule cytoskeletal mechanics facilitates two major GBM therapeutic resistance strategies-diffuse invasion and tumor microtube network formation. Actin and microtubule reorganization is controlled by Rho-GTPases, which exert their effects through downstream effector protein activation, including Rho-associated kinases (ROCK) 1 and 2 and mammalian diaphanous-related (mDia) formins (mDia1, 2, and 3).

Targeting the mDia Formin-Assembled Cytoskeleton Is an Effective Anti-Invasion Strategy in Adult High-Grade Glioma Patient-Derived Neurospheres.

High-grade glioma (HGG, WHO Grade III⁻IV) accounts for the majority of adult primary malignant brain tumors. Failure of current therapies to target invasive glioma cells partly explains the minimal survival advantages: invasive tumors lack easily-defined surgical margins, and are inherently more chemo- and radioresistant. Much work centers upon Rho GTPase-mediated glioma invasion, yet downstream Rho effector roles are poorly understood and represent potential therapeutic targets.

Carcinoma associated fibroblasts (CAFs) promote breast cancer motility by suppressing mammalian Diaphanous-related formin-2 (mDia2).

The tumor microenvironment (TME) promotes tumor cell invasion and metastasis. An important step in the shift to a pro-cancerous microenvironment is the transformation of normal stromal fibroblasts to carcinoma-associated fibroblasts (CAFs). CAFs are present in a majority of solid tumors and can directly promote tumor cell motility via cytokine, chemokine and growth factor secretion into the TME.

SMIFH2-mediated mDia formin functional inhibition potentiates chemotherapeutic targeting of human ovarian cancer spheroids.

Due to a lack of effective screening or prevention protocol for epithelial ovarian cancer (EOC), there is a critical unmet need to develop therapeutic interventions for EOC treatment. EOC metastasis is unique. Initial dissemination is not primarily hematogenous, yet is facilitated through shedding of primary tumor cells into the peritoneal fluid and accumulating ascites.

An mDia2/ROCK signaling axis regulates invasive egress from epithelial ovarian cancer spheroids.

Multi-cellular spheroids are enriched in ascites of epithelial ovarian cancer (OvCa) patients. They represent an invasive and chemoresistant cellular population fundamental to metastatic dissemination. The molecular mechanisms triggering single cell invasive egress from spheroids remain enigmatic.

Congenic strains confirm aerobic running capacity quantitative trait loci on rat chromosome 16 and identify possible intermediate phenotypes.

We previously identified two inbred rat strains divergent for treadmill aerobic running capacity (ARC), the low-performing Copenhagen (COP) and the high-performing DA rats, and used an F(2)(COPxDA) population to identify ARC quantitative trait loci (QTLs) on rat chromosome 16 (RNO16) and the proximal portion of rat chromosome 3 (RNO3). Two congenic rat strains were bred to further investigate these ARC QTLs by introgressing RNO16 and the proximal portion of RNO3 from DA rats into the genetic background of COP rats and were named COP.DA(chr 16) and COP.