Small-molecule agonists of mammalian Diaphanous–related (mDia) formins reveal an effective glioblastoma anti-invasion strategy

Abstract

Formin agonists impede the most dangerous aspect of glioblastoma—tumor spread into surrounding healthy tissue. Formin activation impairs a novel aspect of the transformed cell and informs the development of antitumor strategies for a cancer needing a more effective therapy.

Glioma infiltration and extracellular matrix: key players and modulators

“…Two major effector proteins of RhoA, RhoB, and RhoC GTPases are the mammalian homolog of Drosophila diaphanous (mDia, belonging to the formin protein family) and Rho‐associated coiled‐coil forming kinase (ROCK), which are associated with migration in gliomas (Arden et al, ; Xue et al, ). ROCK has been implicated in the abovementioned nuclear squeezing and glioblastoma cell invasion in ex vivo brain slices (Beadle et al, ).…”

“…In addition, direct cell-cell contacts and especially ECM-receptors drive glioma cell migration and invasion. Key components of this phenomenon are invadopodia, glioma-ECM interactions, and the production of proteases and glycosidases that facilitate invasion by ECM-degradation kinase (ROCK), which are associated with migration in gliomas (Arden et al, 2015;Xue et al, 2016). ROCK has been implicated in the abovementioned nuclear squeezing and glioblastoma cell invasion in ex vivo brain slices (Beadle et al, 2008).…”

High expression of FMNL3 associates with cancer cell migration, invasion, and unfavorable prognosis in tongue squamous cell carcinoma

“…FMNL3 is a newly discovered gene whose encoded product belongs to the DRFs family . Some studies showed that FMNL3 is highly expressed in a variety of malignant tumors and is associated with poor prognosis .…”

“…Its encoded product, FMNL3, is classified among the diaphanous‐related formins (DRFs). DRFs are currently some of the most potent actin nucleation factors and are involved in many actin‐based life processes, including cell adhesion, cell movement, cytokinesis, morphological changes, and formation of cell polarity . As one of the important members of the DRFs subgroup, there are also reports that FMNL3 participates in cell‐cell adhesion and promotes cell migration, promoting the invasion and metastasis of various malignant tumors .…”

“…DRFs are currently some of the most potent actin nucleation factors and are involved in many actin-based life processes, including cell adhesion, cell movement, cytokinesis, morphological changes, and formation of cell polarity. 9,10 As one of the important members of the DRFs subgroup, there are also reports that FMNL3 participates in cell-cell adhesion and promotes cell migration, promoting the invasion and metastasis of various malignant tumors. 11 FMNL3 has recently been shown to be overexpressed in some malignancies, including colorectal cancer, 12 nasopharyngeal carcinoma, 13 and esophageal cancer.…”