Modeling myosin Va liposome transport through actin filament networks reveals a percolation threshold that modulates transport properties.

Myosin Va (myoVa) motors transport membrane-bound cargo through three-dimensional, intracellular actin filament networks. We developed a coarse-grained, in silico model to predict how actin filament density (3-800 filaments) within a randomly oriented actin network affects fluid-like liposome (350 nm vs. 1750 nm) transport by myoVa motors. Five thousand simulated liposomes transported within each network adopted one of three states: transport, tug-of-war, or diffusion. Diffusion due to liposome detachment from actin rarely occurred given at least 10 motors on the liposome surface. However, with increased actin density, liposomes transitioned from primarily directed transport on single actin filaments to an apparent random walk, resulting from a mixture of transport and tug-of-wars as the probability of encountering additional actin filaments increased. This phase transition arises from a percolation phase transition at a critical number of accessible actin filaments, Nc. Nc is a geometric property of the actin network that depends only on the position and polarity of the actin filaments, transport distance, and the liposome diameter, as evidenced by a fivefold increase in liposome diameter resulting in a fivefold decrease in Nc. Thus in cells, actin network density and cargo size may be regulated to match cargo delivery to the cell's physiological demands.

A dynamic Dab2 keeps myosin VI stably on track.

Myosins are actin-based motor proteins known to perform a variety of different mechanical tasks in cells including transporting cargo, generating tension, and linking the cytoskeleton and membrane. Myosins that function as transporters often form complexes with adaptor proteins and vesicular membranes, making it unclear how they transport their cargo through the actin cytoskeletal network. Rai et al. now use single-molecule kinetics, FRET, and DNA origami scaffolds that mimic motor-adaptor complexes to reveal that the myosin VI-Dab2 complex, which is held together weakly and turns over rapidly, can facilitate processive transport without disruption of the cytoskeleton.

Striated myosin heavy chain gene is a crucial regulator of larval myogenesis in the pacific oyster Crassostrea gigas.

Pacific oyster (Crassostrea gigas), the most productive economical bivalve mollusc, is identified as an attractive model for developmental studies due to its classical mosaic developmental pattern. Myosin heavy chain is a structural and functional component of myosin, the key muscle protein of thick filament. Here, full length cDNA of striated myosin heavy chains in C. gigas (CgSmhc) was obtained, and the expression profiles were examined in different development stage. CgSmhc had a high expression level in trochophore and D-shaped stage during embryo-larval stage. In adult, CgSmhc was a muscle-specific gene and primarily expressed in muscle tissues. Then, activity of 5' flanking region of CgSmhc were examined through an reconstructed EGFP vector. The results indicated that 3098 bp 5'-flanking region of CgSmhc owned various conserved binding sites of myogenesis-related regulatory elements, and the 2000 bp 5'-flanking sequence was sufficient to induce the CgSmhc expression. Subsequently, the CRISPR/Cas9-mediated target disruption of CgSmhc was generated by co-injection of Cas9mRNA and CgSmhc-sgRNAs into one-cell stage embryos of C. gigas. Loss of CgSmhc had a visible effect on the sarcomeric organization of thin filaments in larval musculature, indicating that CgSmhc was required during larval myogenesis to regulate the correct assembly of sarcomere.

Fiber-type phenotype of the jaw-closing muscles in Gorilla gorilla, Pan troglodytes, and Pan paniscus: A test of the Frequent Recruitment Hypothesis.

Skeletal muscle fiber types are important determinants of the contractile properties of muscle fibers, such as fatigue resistance and shortening velocity. Yet little is known about how jaw-adductor fiber types correlate with feeding behavior in primates. Compared with chimpanzees and bonobos, gorillas spend a greater percentage of their daily time feeding and shift to herbaceous vegetation when fruits are scarce. We thus used the African apes to test the hypothesis that chewing with unusually high frequency is correlated with the expression in the jaw adductors of a high proportion of type 1 (slow, fatigue-resistant) fibers at the expense of other fiber types (the Frequent Recruitment Hypothesis). We used immunohistochemistry to determine the presence and distribution of the four major myosin heavy chain (MHC) isoforms in the anterior superficial masseter (ASM), superficial anterior temporalis, and deep anterior temporalis of four Gorilla gorilla, two Pan paniscus, and four Pan troglodytes. Serial sections were stained against slow (MHC-1/-α-cardiac) and fast (MHC-2/-M) fibers. Fibers were counted and scored for staining intensity, and fiber cross-sectional areas (CSAs) were measured and used to estimate percentage of CSA of each MHC isoform. Hybrid fibers accounted for nearly 100% of fiber types in the masseter and temporalis of all three species, resulting in three main hybrid phenotypes. As predicted, the gorilla ASM and deep anterior temporalis comprised a greater percentage of CSA of the slower, fatigue-resistant hybrid fiber type, significantly so for the ASM (p = 0.015). Finally, the results suggest that fiber phenotype of the chewing muscles contributes to behavioral flexibility in ways that would go undetected in paleontological studies relying solely on morphology of the bony masticatory apparatus.

Myosin Heavy Chain Composition, Creatine Analogues, and the Relationship of Muscle Creatine Content and Fast-Twitch Proportion to Wilks Coefficient in Powerlifters.

Machek, SB, Hwang, PS, Cardaci, TD, Wilburn, DT, Bagley, JR, Blake, DT, Galpin, AJ, and Willoughby, DS. Myosin heavy chain composition, creatine analogues, and the relationship of muscle creatine content and fast-twitch proportion to Wilks coefficient in powerlifters. J Strength Cond Res 34(11): 3022-3030, 2020-Little data exist on powerlifting-specific skeletal muscle adaptations, and none elucidate sex differences in powerlifters. Powerlifters tend to display higher fast-twitch fiber content and phosphagen system dependence. Nevertheless, it is unknown whether fast-twitch fiber or muscle creatine content are predictive of competitive powerlifting performance (via Wilks coefficient). Twelve actively competing powerlifters (PL; n = 6M/6F; age = 21.3 ± 1.0; 3.0 ± 1.8 year competing; 7.3 ± 6.6 meets attended) and 10 sedentary controls (CON; n = 5M/5F; age = 19.4 ± 2.0 year) underwent vastus lateralis muscle biopsies and venipuncture to compare the myosin heavy chain (MHC) fiber type and creatine analogue profiles between groups of both sexes, and determine whether MHC IIa and muscle total creatine (MTC) composition predict powerlifting performance. Samples were analyzed for specific MHC isoform (I, IIa, and IIx) content via mixed homogenate SDS-PAGE, and creatine analogues (MTC, muscle creatine transporter [SLC6A8], serum total creatine [STC], and serum creatinine [CRT]). Furthermore, MHC IIa and MTC content were compared with Wilks coefficient using Pearson correlation coefficients. Male PL MHC content was 50 ± 6% I, 45 ± 6% IIa, and 5 ± 11% IIx, versus 46 ± 6% I, 53 ± 6 IIa, and 0% IIx in female PL. Conversely, male CON MHC content was 33 ± 5% I, 38 ± 7% IIa, and 30 ± 8% IIx, vs. 35 ± 9% I, 44 ± 8% IIa, and 21 ± 17% IIx in female CON. Muscle total creatine, SLC6A8, STC, and CRT did not significantly differ between groups nor sexes. Finally, neither MHC IIa content (r = -0.288; p = 0.364) nor MTC (r = 0.488; p = 0.108) significantly predicted Wilks coefficient, suggesting these characteristics alone do not determine powerlifting skill variation.

Conditional Myh9 and Myh10 inactivation in adult mouse renal epithelium results in progressive kidney disease.

Actin-associated nonmuscle myosin II (NM2) motor proteins play critical roles in a myriad of cellular functions, including endocytosis and organelle transport pathways. Cell type-specific expression and unique subcellular localization of the NM2 proteins, encoded by the Myh9 and Myh10 genes, in the mouse kidney tubules led us to hypothesize that these proteins have specialized functional roles within the renal epithelium. Inducible conditional knockout (cKO) of Myh9 and Myh10 in the renal tubules of adult mice resulted in progressive kidney disease. Prior to overt renal tubular injury, we observed intracellular accumulation of the glycosylphosphatidylinositol-anchored protein uromodulin (UMOD) and gradual loss of Na+ K+ 2Cl- cotransporter from the apical membrane of the thick ascending limb epithelia. The UMOD accumulation coincided with expansion of endoplasmic reticulum (ER) tubules and activation of ER stress and unfolded protein response pathways in Myh9&10-cKO kidneys. We conclude that NM2 proteins are required for localization and transport of UMOD and loss of function results in accumulation of UMOD and ER stress-mediated progressive renal tubulointerstitial disease. These observations establish cell type-specific role(s) for NM2 proteins in regulation of specialized renal epithelial transport pathways and reveal the possibility that human kidney disease associated with MYH9 mutations could be of renal epithelial origin.

Nonmuscle myosin-2 contractility-dependent actin turnover limits the length of epithelial microvilli.

Brush border microvilli enable functions that are critical for epithelial homeostasis, including solute uptake and host defense. However, the mechanisms that regulate the assembly and morphology of these protrusions are poorly understood. The parallel actin bundles that support microvilli have their pointed-end rootlets anchored in a filamentous meshwork referred to as the "terminal web." Although classic electron microscopy studies revealed complex ultrastructure, the composition and function of the terminal web remain unclear. Here we identify nonmuscle myosin-2C (NM2C) as a component of the terminal web. NM2C is found in a dense, isotropic layer of puncta across the subapical domain, which transects the rootlets of microvillar actin bundles. Puncta are separated by ∼210 nm, the expected size of filaments formed by NM2C. In intestinal organoid cultures, the terminal web NM2C network is highly dynamic and exhibits continuous remodeling. Using pharmacological and genetic perturbations in cultured intestinal epithelial cells, we found that NM2C controls the length of growing microvilli by regulating actin turnover in a manner that requires a fully active motor domain. Our findings answer a decades-old question on the function of terminal web myosin and hold broad implications for understanding apical morphogenesis in diverse epithelial systems.

IL-33/IL1RL1 axis regulates cell survival through the p38 MAPK pathway in acute myeloid leukemia.

Acute myeloid leukemia (AML) is often characterized by the presence of specific and recurrent chromosomal abnormalities. Current treatments have greatly increased remission rate, but relapse still occurs. Therefore, novel therapeutic approaches are required. Previously, using a conditional Cbfb-MYH11 knockin mouse model, we showed that Cbfb-MYH11 induces the expression of a cytokine receptor, IL1RL1. Treatment with IL-33, the only known ligand of IL1RL1, promotes leukemia cell survival in vitro. We further found that IL1RL1+ cells survive better with chemotherapy than IL1RL1- population. However, the mechanism is not clear. Here, we show that IL-33 treatment decreased drug sensitivity in the human inv(16) AML cell line ME-1. By RT-PCR, we found that IL-33 increased the expression of IL-4 and IL-6 and led to the activation of both p38 MAPK and NF-κB. We also showed that IL-33 decreased apoptosis with increased phosphorylation of p38 MAPK. Moreover, pre-treatment with MAPK inhibitor attenuated the phosphorylation of p38 enhanced by IL-33 and reversed the anti-apoptotic effect by IL-33. Taken together, our findings give news insights into the potential mechanism of the anti-apoptotic effect by IL-33/IL1RL1 axis in AML which will help in future drug development.

Altered mitochondrial trafficking as a novel mechanism of cancer metastasis.

BACKGROUND: Mammalian cells must constantly reprogram the distribution of mitochondria in order to meet the local demands for energy, calcium, redox balance, and other mitochondrial functions. Mitochondrial localization inside the cell is a result of a combination of movement along the microtubule tracks plus anchoring to actin filaments. RECENT FINDINGS: Recent advances show that subcellular distribution of mitochondria can regulate tumor cell growth, proliferation/motility plasticity, metastatic competence, and therapy responses in tumors. In this review, we discuss our current understanding of the mechanisms by which mitochondrial subcellular distribution is regulated in tumor cells. CONCLUSIONS: Mitochondrial trafficking is dysregulated in tumors. Accumulation of mitochondria at the leading edge of the cell supports energy expensive processes of focal adhesion dynamics, cell membrane dynamics, migration, and invasion.

The people behind the papers.

Myosin is a major component of the sarcomeres of muscle, but its roles during muscle development are still relatively poorly understood. A new paper in Development investigates the function of a developmentally expressed myosin heavy chain isoform during mice myogenesis. We caught up with the paper's four co-first authors, Megha Agarwal, Akashi Sharma, Pankaj Kumar and Amit Kumar, and their supervisor Sam Mathew (Associate Professor in the Regional Centre for Biotechnology in Faridabad, India) to find out more about the project.

Myosin heavy chain-embryonic regulates skeletal muscle differentiation during mammalian development.

Myosin heavy chain-embryonic (MyHC-emb) is a skeletal muscle-specific contractile protein expressed during muscle development. Mutations in MYH3, the gene encoding MyHC-emb, lead to Freeman-Sheldon and Sheldon-Hall congenital contracture syndromes. Here, we characterize the role of MyHC-emb during mammalian development using targeted mouse alleles. Germline loss of MyHC-emb leads to neonatal and postnatal alterations in muscle fiber size, fiber number, fiber type and misregulation of genes involved in muscle differentiation. Deletion of Myh3 during embryonic myogenesis leads to the depletion of the myogenic progenitor cell pool and an increase in the myoblast pool, whereas fetal myogenesis-specific deletion of Myh3 causes the depletion of both myogenic progenitor and myoblast pools. We reveal that the non-cell-autonomous effect of MyHC-emb on myogenic progenitors and myoblasts is mediated by the fibroblast growth factor (FGF) signaling pathway, and exogenous FGF rescues the myogenic differentiation defects upon loss of MyHC-emb function in vitro Adult Myh3 null mice exhibit scoliosis, a characteristic phenotype exhibited by individuals with Freeman-Sheldon and Sheldon-Hall congenital contracture syndrome. Thus, we have identified MyHC-emb as a crucial myogenic regulator during development, performing dual cell-autonomous and non-cell-autonomous functions.This article has an associated 'The people behind the papers' interview.

LncRNA HULC promotes the progression of gastric cancer by regulating miR-9-5p/MYH9 axis.

Long non-coding RNAs (lncRNAs) highly upregulated in liver cancer (HULC) has been identified as an oncogene involved in many human cancers. Herein, we aimed to further explore the role and molecular mechanism of HULC in gastric cancer (GC) progression. The levels of HULC, miR-9-5p and myosin heavy chain 9 (MYH9) mRNA were detected by qRT-PCR. The targeted interaction between HULC and miR-9-5p was verified by dual-luciferase reporter and RNA pull-down assays. Cell proliferation assay, cell colony formation, flow cytometry and transwell assay were used to determine cell proliferation, colony formation, apoptosis and migration and invasion, respectively. Xenograft assay was used to observe the effect of HULC on GC growth in vivo. Our results revealed that HULC was upregulated and miR-9-5p was downregulated in GC, and both were associated with clinicopathologic features of GC patients. A positive correlation was found between HULC expression and epithelial-to-mesenchymal transition (EMT) of GC tissues. Moreover, HULC repressed miR-9-5p expression by binding to miR-9-5p. The regulatory effects of HULC knockdown on GC cell proliferation, migration, invasion, EMT and apoptosis were reversed by introduction of anti-miR-9-5p. HULC regulated MYH9 expression by acting as a molecular sponge of miR-9-5p in GC cells. HULC knockdown inhibited tumor growth in vivo. In conclusion, our data demonstrated that HULC knockdown repressed GC progression at least partly by regulating miR-9-5p/MYH9 axis.

Single-muscle fiber contractile properties in lifelong aerobic exercising women.

The purpose of this study was to examine the effects of lifelong aerobic exercise on single-muscle fiber performance in trained women (LLE; n = 7, 72 ± 2 yr) by comparing them to old healthy nonexercisers (OH; n = 10, 75 ± 1 yr) and young exercisers (YE; n = 10, 25 ± 1 yr). On average, LLE had exercised ~5 days/wk for ~7 h/wk over the past 48 ± 2 yr. Each subject had a vastus lateralis muscle biopsy to examine myosin heavy chain (MHC) I and IIa single-muscle fiber size and function (strength, speed, power). MHC I fiber size was similar across all three cohorts (YE = 5,178 ± 157, LLE = 4,983 ± 184, OH = 4,902 ± 159 µm2). MHC IIa fiber size decreased (P < 0.05) 36% with aging (YE = 4,719 ± 164 vs. OH = 3,031 ± 153 µm2), with LLE showing a similar 31% reduction (3,253 ± 189 µm2). LLE had 17% more powerful (P < 0.05) MHC I fibers and offset the 18% decline in MHC IIa fiber power observed with aging (P < 0.05). The LLE contractile power was driven by greater strength (+11%, P = 0.056) in MHC I fibers and elevated contractile speed (+12%, P < 0.05) in MHC IIa fibers. These data indicate that lifelong exercise did not benefit MHC I or IIa muscle fiber size. However, LLE had contractile function adaptations that enhanced MHC I fiber power and preserved MHC IIa fiber power through different contractile mechanisms (strength vs. speed). The single-muscle fiber contractile properties observed with lifelong aerobic exercise are unique and provide new insights into aging skeletal muscle plasticity in women at the myocellular level.NEW & NOTEWORTHY This is the first investigation to examine the effects of lifelong exercise on single-muscle fiber physiology in women. Nearly 50 yr of moderate to vigorous aerobic exercise training resulted in enhanced slow-twitch fiber power primarily by increasing force production, whereas fast-twitch fiber power was preserved primarily by increasing contractile speed. These unique muscle fiber power profiles helped offset the effects of fast-twitch fiber atrophy and highlight the benefits of lifelong aerobic exercise for myocellular health.

Stiffness of Cargo-Motor Linkage Tunes Myosin VI Motility and Response to Load.

We examine the effect of cargo-motor linkage stiffness on the mechanobiological properties of the molecular motor myosin VI. We use the programmability of DNA nanostructures to modulate cargo-motor linkage stiffness and combine it with high-precision optical trapping measurements to measure the effect of linkage stiffness on the motile properties of myosin VI. Our results reveal that a stiff cargo-motor linkage leads to shorter step sizes and load-induced anchoring of myosin VI, while a flexible linkage results in longer steps with frequent detachments from the actin filament under load. Our findings suggest a novel regulatory mechanism for tuning the dual cellular roles of the anchor and transporter ascribed to myosin VI.

Reconstitution reveals how myosin-VI self-organises to generate a dynamic mechanism of membrane sculpting.

One enigma in biology is the generation, sensing and maintenance of membrane curvature. Curvature-mediating proteins have been shown to induce specific membrane shapes by direct insertion and nanoscopic scaffolding, while the cytoskeletal motors exert forces indirectly through microtubule and actin networks. It remains unclear, whether the manifold direct motorprotein-lipid interactions themselves constitute another fundamental route to remodel the membrane shape. Here we show, combining super-resolution-fluorescence microscopy and membrane-reshaping nanoparticles, that curvature-dependent lipid interactions of myosin-VI on its own, remarkably remodel the membrane geometry into dynamic spatial patterns on the nano- to micrometer scale. We propose a quantitative theoretical model that explains this dynamic membrane sculpting mechanism. The emerging route of motorprotein-lipid interactions reshaping membrane morphology by a mechanism of feedback and instability opens up hitherto unexplored avenues of membrane remodelling and links cytoskeletal motors to early events in the sequence of membrane sculpting in eukaryotic cell biology.

Increase in muscle power is associated with myofibrillar ATPase adaptations during resistance training.

NEW FINDINGS: What is the central question of this study? The aim of this study was to examine the effects of resistance training on gains in the external mechanical power output developed during climbing and myofibrillar ATPase activity in rats. What is the main finding and its importance? Using rapid flow quench experiments, we show that resistance training increases both the power output and the myofibrillar ATPase activity in the flexor digitorum profundus, biceps and deltoid muscles. Data fitting reveals that these functional ameliorations are explained by an increase in the rate constant of liberation of ATP hydrolysis products and contribute to performance gains. ABSTRACT: Skeletal muscle shows a remarkable plasticity that permits functional adaptations in response to different stimulations. To date, modifications of the proportions of myosin heavy chain (MHC) isoforms and increases in fibre size are considered to be the main factors providing sarcomeric plasticity in response to exercise training. In this study, we investigated the effects of a resistance training protocol on the myofibrillar ATPase (m-ATPase) cycle, muscle performance (power output) and MHC gene expression. For this purpose, 8-week-old Wistar Han rats were subjected to 4 weeks of resistance training, with five sessions per week. Muscle samples of flexor digitorum profundus (FDP), biceps and deltoid were collected and subjected to RT-qPCR analyses and assessment of m-ATPase activity with rapid flow quench apparatus. Training led to a significant increase in muscle mass, except for the biceps, and in total mechanical power output (+135.7%, P < 0.001). A shift towards an intermediate fibre type (i.e. MHC2x-to-MHC2a isoform transition) was also observed in biceps and FDP but not in the deltoid muscle. Importantly, rapid flow quench experiments revealed an enhancement of the m-ATPase activity during contraction at maximal velocity (kF ) in the three muscles, with a more marked effect in FDP (+242%, P < 0.001). Data fitting revealed that the rate constant of liberation of ATP hydrolysis products (k3 ) appears to be the main factor influencing the increase in m-ATPase activity. In conclusion, the data showed that, in addition to classically observed changes in MHC isoform content and fibre hypertrophy, m-ATPase activity is enhanced during resistance training and might contribute significantly to performance gains.

A humanized mouse model, demonstrating progressive hearing loss caused by MYO6 p.C442Y, is inherited in a semi-dominant pattern.

Myosin VI is an actin-associated molecular motor vital for auditory and vestibular function. It is encoded by MYO6 located on chromosome 6q13 in human. Pathogenic variants in MYO6 have been associated with both dominant and recessive forms of hearing loss. However, the molecular mechanisms remain unclear. We established a humanized knock-in mouse model, Myo6-C442Y, to mimic the p.C442Y missense variant identified in human patients with autosomal dominant nonsyndromic hearing loss designated as DFNA22. We characterized hearing and inner ear morphologies of Myo6-C442Y and wild-type control mice. We found that both homozygous and heterozygous Myo6-C442Y mice exhibited hearing loss from three weeks after birth that rapidly progressed to profound deafness by six to nine weeks of age. The hearing loss corresponded to the degeneration of hair cells in the organ of Corti. We also observed disorganized stereocilia with irregular morphological features by immunohistochemistry and scanning electron microscopy. Additionally, hearing loss and inner-ear morphological anomalies were more pronounced and deteriorated more drastically in homozygous than in heterozygous Myo6-C442Y mice, indicating a semi-dominant inheritance pattern. Heterozygous Myo6-C442Y mice recapitulated the progressive postlingual sensorineural deafness in human, thus providing a useful model for elucidating the role myosin VI plays in the mammalian auditory system. Furthermore, the late-onset hearing loss of this mouse model may provide a therapeutic window for the emerging gene therapy, a promising strategy to treat certain forms of genetic deafness.

Angiotensin II-mediated MYH9 downregulation causes structural and functional podocyte injury in diabetic kidney disease.

MYH9, a widely expressed gene encoding nonmuscle myosin heavy chain, is also expressed in podocytes and is associated with glomerular pathophysiology. However, the mechanisms underlying MYH9-related glomerular diseases associated with proteinuria are poorly understood. Therefore, we investigated the role and mechanism of MYH9 in diabetic kidney injury. MYH9 expression was decreased in glomeruli from diabetic patients and animals and in podocytes treated with Ang II in vitro. Ang II treatment and siRNA-mediated MYH9 knockdown in podocytes resulted in actin cytoskeleton reorganization, reduced cell adhesion, actin-associated protein downregulation, and increased albumin permeability. Ang II treatment increased NOX4 expression and ROS generation. The Ang II receptor blocker losartan and the ROS scavenger NAC restored MYH9 expression in Ang II-treated podocytes, attenuated disrupted actin cytoskeleton and decreased albumin permeability. Furthermore, MYH9 overexpression in podocytes restored the effects of Ang II on the actin cytoskeleton and actin-associated proteins. Ang II-mediated TRPC6 activation reduced MYH9 expression. These results suggest that Ang II-mediated MYH9 depletion in diabetic nephropathy may increase filtration barrier permeability by inducing structural and functional podocyte injury through TRPC6-mediated Ca2+ influx by NOX4-mediated ROS generation. These findings reveal a novel MYH9 function in maintaining urinary filtration barrier integrity. MYH9 may be a potential target for treating diabetic nephropathy.

NMIIA promotes tumor growth and metastasis by activating the Wnt/ß-catenin signaling pathway and EMT in pancreatic cancer.

Non-muscle myosin IIA (NMIIA) protein plays an important role in cell cytokinesis and cell migration. The role and underlying regulatory mechanisms of NMIIA in pancreatic cancer (PC) remain elusive. We found that NMIIA is highly expressed in PC tissues and contributes to PC poor progression by using open microarray datasets from the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and PC tissue arrays. NMIIA regulates ß-catenin mediated EMT to promote the proliferation, migration, invasion, and sphere formation of PC cells in vitro and in vivo. NMIIA controls the ß-catenin transcriptional activity by interacting with ß-catenin. Moreover, MEK/ERK signaling is critical in MLC2 (Ser19) phosphorylation, which can mediate NMIIA activity and regulate Wnt/ß-catenin signaling. These findings highlight the significance of NMIIA in tumor regression and implicate NMIIA as a promising candidate for PC treatment.

Myosin Heavy Chain 9: Oncogene or Tumor Suppressor Gene?

MYH9 was first discovered due to thrombocytopenia caused by MYH9 mutation-related abnormalities. In recent years, researchers have increasingly found that MYH9 plays an important role in cancer as a cytokine involved in cytoskeletal reorganization, cellular pseudopodia formation, and migration. MYH9 is closely related to the progress and poor prognosis of most solid tumors, and it is now accepted that MYH9 is a suppressor gene and plays an important role on the re-Rho pathway. Recent research has been limited to the study of tissues. However, it would be more direct and informative to be able to use hematology to assess tumor prognosis and changes in MYH9 levels and NMMHC-IIA. This article summarizes recent research on MYH9 and provides a reference for future clinical research.