Formins in Human Disease

Abstract

Almost 25 years have passed since a mutation of a formin gene, DIAPH1, was identified as being responsible for a human inherited disorder: a form of sensorineural hearing loss. Since then, our knowledge of the links between formins and disease has deepened considerably. Mutations of DIAPH1 and six other formin genes (DAAM2, DIAPH2, DIAPH3, FMN2, INF2 and FHOD3) have been identified as the genetic cause of a variety of inherited human disorders, including intellectual disability, renal disease, peripheral neuropathy, thrombocytopenia, primary ovarian insufficiency, hearing loss and cardiomyopathy. In addition, alterations in formin genes have been associated with a variety of pathological conditions, including developmental defects affecting the heart, nervous system and kidney, aging-related diseases, and cancer. This review summarizes the most recent discoveries about the involvement of formin alterations in monogenic disorders and other human pathological conditions, especially cancer, with which they have been associated. In vitro results and experiments in modified animal models are discussed. Finally, we outline the directions for future research in this field.

Small Extracellular Vesicles and Their Involvement in Cancer Resistance: An Up-to-Date Review

“…CEBPG is involved in the pathogenesis of conditions such as acute myeloid leukemia, esophageal cancer, and lung cancer [ 103 , 104 , 105 ]. Similar properties are attributed to FMNL3 [ 106 , 107 ], a high expression of which is associated with poor prognosis in patients with colorectal carcinoma, melanoma, or tongue cancer [ 108 , 109 , 110 , 111 ]. Moreover, exosomal circ_0000337 enhances the cisplatin resistance of esophageal cancer cells by increasing Janus kinase 2 (JAK2) expression due to miR-377-3p inhibition [ 48 ].…”

Actin- and microtubule-based motors contribute to clathrin-independent endocytosis in yeast

“…To date, homologues of several yeast CIE proteins have been linked to disease. For example, mutations in diaphanous-related formins, which are homologous to yeast Bni1, are associated with microcephaly and related developmental disorders ( Labat-de-Hoz and Alonso, 2021 ). From our current study, Pac1 is related to the lissencephaly related protein LIS1, while Kar9 is related to the APC protein involved in colorectal cancer ( Geiser et al.…”

Role of Cytoskeletal Diaphanous-Related Formins in Hearing Loss

“…The cellular and molecular functions of DRFs have been extensively studied and are reviewed elsewhere [ 2 , 3 ]. An overview of the involvement of DRFs and other formin subfamilies in human diseases has also recently been published [ 4 ].…”