Tumor Cell Dependence on Ran-GTP–Directed Mitosis

Abstract

Deregulated cell division is a hallmark of cancer, but whether tumor cells become dependent on specific mitotic mechanisms is not known. Here, we show that the small GTPase Ran, a regulator of mitotic spindle formation, is differentially overexpressed in human cancer as compared with normal tissues, in vivo.

MiRNA-29a regulates the expression of numerous proteins and reduces the invasiveness and proliferation of human carcinoma cell lines

“…33 Also, Xia and colleagues found that acute silencing of RAN in various tumour cell types causes aberrant mitotic spindle formation, mitochondrial dysfunction and apoptosis. 34 This dependency was not reflected in other normal cell types.…”

“…Indeed, the RAN-dependent status of many tumours 34 raises the possibility of augmenting miR-29a expression as a potential therapeutic intervention.…”

Tumor suppressor function of miR-483-3p on squamous cell carcinomas due to its pro-apoptotic properties

“…Overexpression of RAN is associated with poor patient outcome in ovarian, breast, and lung cancers, and its knockdown results in mitotic defects and apoptosis. [46][47][48] Moreover, RAN and survivin form complexes that were shown to be crucial for mitotic spindle formation and chromosome segregation in tumor cells. 49 Interestingly, RAN is also targeted by miR-203, whose expression is decreased in healing epidermis, thus favoring keratinocytes migration and proliferation.…”

Nano-encapsulation of a novel anti-Ran-GTPase peptide for blockade of regulator of chromosome condensation 1 (RCC1) function in MDA-MB-231 breast cancer cells

“…Therefore, an awareness and understanding of target pathways is essential to the development of novel therapeutics. Specifically, recent studies show that Ran (Ras-related nuclear) protein is involved in growth regulation, apoptotic resistance, tumour transformation, increased aggressiveness and enhanced metastasis in a wide range of tumour types, such as breast, and is, therefore, a potential therapeutic target (Abe et al, 2008;Kurisetty et al, 2008;Ly et al, 2010;Xia et al, 2008;Yuen et al, 2012).…”