Cytoskeletons (F-actin) and spermatogenesis
C. Yan Cheng in Spermatogenesis, 2018
The forces generated by actin filaments and networks, as well as those generated during myosin-mediated movements, create a mechanically-sensitive dynamic state, reviewed in De La Cruz and Gardel 2015.10 This mechanically sensitive state allows the cell to respond to external stimuli, for example to shear stress, but also to respond to internal cues such as forces generated within the cytoskeleton itself. Depending on the type of filament cross-linking and the abundance of myosin motors, the actin network can be arranged into various higher-order structures with different physical properties. For example, cell motility is achieved by the polymerization of branched actin filaments in lamellipodia effectively pushing the leading edge of a migrating cell forward. Actin networks can be contractile; actomyosin (actin + myosin complex)-mediated contractility is involved in many cellular functions such as exo- and endocytosis and cell shape changes. Actin networks can also be organized into ring structures; constricting actomyosin rings create the cleavage furrow between dividing cells and facilitate cytokinesis, and stabilizing actin rings are components of cell adhesion junctions.11
ANLN, Regulated by SP2, Promotes Colorectal Carcinoma Cell Proliferation via PI3K/AKT and MAPK Signaling Pathway
Published in Journal of Investigative Surgery, 2022
Yanwei Liu, Pengwei Cao, Feng Cao, Song Wang, Yan He, Yanyan Xu, Yong Wang
Located on chromosome 7q14.2, anillin is a universally expressed gene that encodes Anillin (ANLN), an actin-binding protein that contains regions for F-actin and myosin binding and a conserved C-terminal PH domain [3]. ANLN mainly functions in the nucleus during interphase and then transports to the cytoplasm after the initiation of mitosis [4]. In the cytoplasm, ANLN is gathered in the cleavage furrow and contractile ring in telophase, and the process is mediated in a RhoA-dependent manner [5]. Research has shown that dysregulated ANLN is related to the onset of various carcinomas, such as breast, ovarian, and lung cancers [6–8]. ANLN knockdown in human lung cancer cells impaired tumor growth in a mouse model [8]. ANLN silencing inhibited both cell migration and colony formation activities of breast cancer cells [6]. Although one report has been published about ANLN in CRC, the authors mainly focused on the role of ANLN as either a biomarker or a prognosis indicator for patients with CRC [9]. The function and mechanism of ANLN in CRC progression thus remain unknown.
Tumor treating fields: a comprehensive overview of the underlying molecular mechanism
Published in Expert Review of Molecular Diagnostics, 2022
Pengjie Hong, Nijiati Kudulaiti, Shuai Wu, Jingtao Nie, Dongxiao Zhuang
The primary mechanism of action of TTFields is to stall tumor cell proliferation, which requires accurate alignment of tubulin and septin. As reported by Giladi et al., a decreased ratio of polymerized to total tubulin and abnormal spindle geometry can be found in TTFields-treated cells, resulting in disrupted mitotic spindle formation during metaphase [19]. Such spindle damage will activate the spindle assembly checkpoint (SAC), which prevents erroneous segregation of sister chromatids, leading to prolonged mitotic arrest and the eventual cell death (Figure 1) [19,20]. In addition to α/β-tubulin, the functional unit of microtubule polymerization with high dipole moment, the mitotic septin complex was also dynamically relocalized at the late stages of the cell cycle. The septin complex consists of septins 2, 6, and 7, and plays a critical role in the localization and function of the cytokinetic cleavage furrow (CCF) [14]. TTFields reportedly perturb the normal localization of the septin complex to the anaphase spindle midline and the CCF, thereby disrupting cell division (Figure 1). Moreover, it was also suggested that electric fields become highly inhomogeneous at the mitotic furrow at the telophase/cytokinesis stage, exerting dielectrophoretic effects on biomolecules and altering the normal functions of cellular components (Figure 1). Such events compromise cell division subsequently via the induction of violent plasma membrane contractions [21]. Thus, the aberrant localization and function of contractile elements and the subsequent formation of ectopic furrows can cause membrane blebbing during mitosis upon TTFields treatment, further impairing cancer cell viability.
Ultra-long silver nanowires induced mitotic abnormalities and cytokinetic failure in A549 cells
Published in Nanotoxicology, 2019
Fengbang Wang, Ying Chen, Yuanyuan Wang, Yongguang Yin, Guangbo Qu, Maoyong Song, Hailin Wang
Cytokinetic failure and multipolar mitosis are mechanisms that lead to aneuploidy, which is a hallmark of cultured cells from many types of cancer (Ganem et al. 2007; Negrini, Gorgoulis, and Halazonetis 2010; Lv et al. 2012; Santaguida and Amon 2015). Indeed, the formation of multinucleated cells is also a key characteristic of senescence (Sliwinska et al. 2009; Vergel et al. 2010; Dikovskaya et al. 2015). Multinucleated senescent melanocytes may harbor genome instability, a risk factor of malignancy, and these cells have been proposed to give rise to highly proliferative, tumor-initiating stem-like cells (Fox and Duronio 2013). Aneuploidy was also recently observed in both tumors induced by asbestos fibers in vivo and in vitro (Craighead et al. 1987; MacCorkle et al. 2006; Cortez and Machado-Santelli 2008). It has been validated that asbestos fibers can be trapped by the cleavage furrow and lead to aneuploidy through cytokinetic regression and multipolar division(Jensen et al. 1996; Cortez et al. 2016; Zhang, Lv et al. 2017). In this study, ultra-long AgNWs induced cytokinesis failure and multipolar mitosis, even after the formation of long cytoplasmic bridges, and resulted in the retraction of the bridge and reversal of the cleavage furrow to form aneuploidy. These results highlight the carcinogenic risks of ultra-long AgNWs as asbestos fibers. Furthermore, other ultra-long nanofibers should also be carefully investigated before widely produced and used. The induction of mitotic abnormalities and cytokinetic failure provides an important indicator of carcinogenic risk for further safety studies related with nanofibers. Also, due to the constructional complexity, further toxicity studies of AgNWs and other nanofibers should concern more aspects, such as length, diameter, shape, density, curvature, dose, and coating.
Related Knowledge Centers
- Actin
- Cell Biology
- Cell Division
- Cytoskeleton
- Golgi Apparatus
- Microtubule
- Myosin
- Cell Membrane
- Cytokinesis
- Actomyosin Ring