Ezrin gone rogue in cancer progression and metastasis: An enticing therapeutic target

Barik, Ganesh Kumar; Sahay, Osheen; Paul, Debasish; Santra, Manas Kumar

doi:10.1016/j.bbcan.2022.188753

Cited by 16 publications

(18 citation statements)

References 303 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Phosphorylation is currently the most well-studied post-translational modification of ezrin ( Michie et al, 2019 ). Among the reported phosphorylation sites, T567, S535 and S536 are located at the C-ERMAD terminus, of which T567 is the most studied phosphorylation site ( Xue et al, 2020 ); Y477 is located in the Linker region; Y424, Y353, S413, T468 exist in the α-helical domain; N-ERMAD terminus contains S66(F1), Y145(F2), Y146(F2), T235(F3), Y291(F3) ( Figure 2A ) ( Michie et al, 2019 ; García-Ortiz and Serrador, 2020 ; Barik et al, 2022 ).…”

Section: The Post-translational Modifications Of Ezrinmentioning

confidence: 99%

“…1981, Hunter et al discovered rapid phosphorylation of tyrosine residue of an approximately 81 kD polypeptide, the first time that ezrin was discovered as a substrate for the epidermal growth factor receptor protein tyrosine kinase. In 1983, an 80 kD protein was purified during identifying the microvilli fraction and named ezrin after the university (Ezra Cornell) ( Barik et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

“…Ezrin protein also participates in cell adhesion and can form complexes on the cell surface with various cell adhesion molecules such as CD44, E-calmodulin, and integrin, which are involved in cell adhesion, deformation, and migration by regulating actin shape ( Figures 1B, C ) ( Distel et al, 2022 ). Ezrin has been extensively studied in the field of tumorigenesis, with research focusing on its role in regulating cell migration, proliferation, differentiation, and apoptosis, as well as mediating cell-cell signaling to control tumor growth, differentiation, and apoptosis ( Barik et al, 2022 ). In some biological processes of female reproduction, such as endometrial hyperplasia and embryo implantation, tumor-like biological properties exist ( Li et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Ezrin expression in female reproductive tissues: A review of regulation and pathophysiological implications

Shi²,

Xu³

et al. 2023

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Ezrin, a plasma membrane-microfilament linker, is a cytoskeletal organizer involved in many cellular activities by binding to the membrane protein-ezrin-cytoskeletal protein complex and regulating downstream signal transduction. Increasing evidence demonstrates that ezrin plays an important role in regulating cell polarity, proliferation and invasion. In this study, we analyzed the effects of ezrin on oocytes, follicle development, embryo development and embryo implantation. We reviewed the recent studies on the modalities of ezrin regulation and its involvement in the biological processes of female reproductive physiology and summarized the current research advances in ezrin inhibitors. These studies will provide new strategies and insights for the treatment of diseases.

show abstract

Section: The Post-translational Modifications Of Ezrinmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Ezrin expression in female reproductive tissues: A review of regulation and pathophysiological implications

Shi²,

Xu³

et al. 2023

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…In mice, ERM inhibition prevents breast cancer or osteosarcoma cell metastasis (Elliott et al, 2005;Ghaffari et al, 2019). These examples and other observations led to the concept that ERMs play central roles in metastasis (Barik et al, 2022;Curto and McClatchey, 2004). ERMs are, therefore, attractive targets for anti-cancer therapies.…”

Section: Introductionmentioning

confidence: 99%

“…The C-ERMAD also harbors a conserved regulatory threonine residue (T567, T564, and T558 in ezrin, radixin, and moesin, respectively) that is phosphorylated upon stimulation to maintain the active open conformation (Simons et al, 1998). ERMs were shown to control cell morphogenesis during mitosis (Carreno et al, 2008; De Jamblinne et al, 2020; Kunda et al, 2008; Leguay et al, 2022; Roubinet et al, 2011), cell migration (Arpin et al, 2011; Barik et al, 2022; Hoskin et al, 2015) and cell invasion (Estecha et al, 2009; Song et al, 2020). In a pathological context, high levels of ezrin, radixin, or moesin expression correlate with a high rate of metastasis and poor prognosis in several cancers (Clucas and Valderrama, 2014).…”

Section: Introductionmentioning

confidence: 99%

The G protein-coupled receptor TBXA2R activates ERMs to control cell motility and invasion of triple-negative breast cancer cells.

Leguay

Naffati

et al. 2023

Preprint

View full text Add to dashboard Cite

Metastasis, the process by which cancer cells colonize distant organs, relies on the ability of these cells to migrate and invade the surrounding tissues. The ezrin, radixin, and moesin family (ERM) of proteins are critical regulators of cell morphology transformations required for cancer cell movement and invasion. Yet, how ERMs are activated during metastasis remains poorly understood. Here, we identified the thromboxane A2 receptor (TBXA2R), a G protein-coupled receptor, as a critical activator of ERMs that promotes motility, invasion, and metastasis of triple-negative breast cancer (TNBC) cells. We found that ERM activation downstream of TBXA2R signaling depends on the Gαq/11 and Gα12/13 subfamilies, the small GTPase RhoA, and its Ser/Thr kinase effector SLK. We also showed that TBXA2R signaling increases TNBC cell motility and invasion in vitro and metastasis in vivo, depending on ERMs. These findings unveil a novel mechanism by which a member of the largest class of receptors activates key metastatic determinants to promote TNBC metastasis, which could have important implications for developing novel therapeutic strategies.

show abstract

Mechanotransduction and epigenetic modulations of chromatin: Role of mechanical signals in gene regulation

Mishra,

Chakraborty,

Niharika

et al. 2024

J of Cellular Biochemistry

View full text Add to dashboard Cite

Mechanical forces may be generated within a cell due to tissue stiffness, cytoskeletal reorganization, and the changes (even subtle) in the cell's physical surroundings. These changes of forces impose a mechanical tension within the intracellular protein network (both cytosolic and nuclear). Mechanical tension could be released by a series of protein–protein interactions often facilitated by membrane lipids, lectins and sugar molecules and thus generate a type of signal to drive cellular processes, including cell differentiation, polarity, growth, adhesion, movement, and survival. Recent experimental data have accentuated the molecular mechanism of this mechanical signal transduction pathway, dubbed mechanotransduction. Mechanosensitive proteins in the cell's plasma membrane discern the physical forces and channel the information to the cell interior. Cells respond to the message by altering their cytoskeletal arrangement and directly transmitting the signal to the nucleus through the connection of the cytoskeleton and nucleoskeleton before the information despatched to the nucleus by biochemical signaling pathways. Nuclear transmission of the force leads to the activation of chromatin modifiers and modulation of the epigenetic landscape, inducing chromatin reorganization and gene expression regulation; by the time chemical messengers (transcription factors) arrive into the nucleus. While significant research has been done on the role of mechanotransduction in tumor development and cancer progression/metastasis, the mechanistic basis of force‐activated carcinogenesis is still enigmatic. Here, in this review, we have discussed the various cues and molecular connections to better comprehend the cellular mechanotransduction pathway, and we also explored the detailed role of some of the multiple players (proteins and macromolecular complexes) involved in mechanotransduction. Thus, we have described an avenue: how mechanical stress directs the epigenetic modifiers to modulate the epigenome of the cells and how aberrant stress leads to the cancer phenotype.

show abstract

Ezrin gone rogue in cancer progression and metastasis: An enticing therapeutic target

Cited by 16 publications

References 303 publications

Ezrin expression in female reproductive tissues: A review of regulation and pathophysiological implications

Ezrin expression in female reproductive tissues: A review of regulation and pathophysiological implications

The G protein-coupled receptor TBXA2R activates ERMs to control cell motility and invasion of triple-negative breast cancer cells.

Mechanotransduction and epigenetic modulations of chromatin: Role of mechanical signals in gene regulation

Contact Info

Product

Resources

About