Myristoylated alanine-rich C kinase substrate (MARCKS): a multirole signaling protein in cancers

Fong, Lon Wolf R.; Yang, David C.H.; Chen, Ching-Hsien

doi:10.1007/s10555-017-9709-6

Cited by 54 publications

(74 citation statements)

References 86 publications

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“…In this study, 3 genes ( NCS1 , SLC44A5 , and MARCKS ) were found to be coordinately controlled by both miR‐144‐5p and miR‐144‐3p in LUSQ cells. MARCKS is a major substrate of protein kinase C . Recent studies have shown that MARCKS plays a pivotal role in cancer development and progression .…”

Section: Discussionmentioning

confidence: 99%

“…27 In this study, 3 genes (NCS1, SLC44A5, and MARCKS) were found to be coordinately controlled by both miR-144-5p and miR-144-3p in LUSQ cells. MARCKS is a major substrate of protein kinase C. 42 Recent studies have shown that MARCKS plays a pivotal role in cancer development and progression. 42 Moreover, in lung cancer, aberrant MARCKS expression was detected in clinical specimens, and MARCKS expression was implicated in this disease.…”

Section: Discussionmentioning

confidence: 99%

“…MARCKS is a major substrate of protein kinase C. 42 Recent studies have shown that MARCKS plays a pivotal role in cancer development and progression. 42 Moreover, in lung cancer, aberrant MARCKS expression was detected in clinical specimens, and MARCKS expression was implicated in this disease. 43,44 Among the 3 targets, we focused on NCS1 because its aberrant expression significantly predicted poor prognosis in patients.…”

Section: Discussionmentioning

confidence: 99%

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Involvement of dual‐strand of the miR‐144 duplex and their targets in the pathogenesis of lung squamous cell carcinoma

et al. 2018

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The prognosis of patients with advanced‐stage lung squamous cell carcinoma (LUSQ) is poor, and effective treatment protocols are limited. Our continuous analyses of antitumor microRNAs (miRNAs) and their oncogenic targets have revealed novel oncogenic pathways in LUSQ. Analyses of our original miRNA expression signatures indicated that both strands of miR‐144 (miR‐144‐5p, the passenger strand; miR‐144‐3p, the guide strand) showed decreased expression in cancer tissues. Additionally, low expression of miR‐144‐5p significantly predicted a poor prognosis in patients with LUSQ by The Cancer Genome Atlas database analyses (overall survival, P = 0.026; disease‐free survival, P = 0.023). Functional assays revealed that ectopic expression of miR‐144‐5p and miR‐144‐3p significantly blocked the malignant abilities of LUSQ cells, eg, cancer cell proliferation, migration, and invasion. In LUSQ cells, 13 and 15 genes were identified as possible oncogenic targets that might be regulated by miR‐144‐5p and miR‐144‐3p, respectively. Among these targets, we identified 3 genes (SLC44A5, MARCKS, and NCS1) that might be regulated by both strands of miR‐144. Interestingly, high expression of NCS1 predicted a significantly poorer prognosis in patients with LUSQ (overall survival, P = 0.013; disease‐free survival, P = 0.048). By multivariate analysis, NCS1 expression was found to be an independent prognostic factor for patients with LUSQ patients. Overexpression of NCS1 was detected in LUSQ clinical specimens, and its aberrant expression enhanced malignant transformation of LUSQ cells. Our approach, involving identification of antitumor miRNAs and their targets, will contribute to improving our understanding of the molecular pathogenesis of LUSQ.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Involvement of dual‐strand of the miR‐144 duplex and their targets in the pathogenesis of lung squamous cell carcinoma

et al. 2018

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“…MARCKS is a membrane-bound protein that functions in various important cellular processes, such as cytoskeletal remodeling, motility, secretion and exocytosis [17]. For instance, MARCKS has been shown to regulate the actin cytoskeleton and, consequently, the number and length of filopodia [18].…”

Section: Introductionmentioning

confidence: 99%

“…For instance, MARCKS has been shown to regulate the actin cytoskeleton and, consequently, the number and length of filopodia [18]. Interestingly, the phosphorylated form of MARCKS has been shown to promote cell motility and membrane protrusions and significantly affect the invasiveness of several cancer cells [17]. However, a possible functional role of the MARCKS protein in WNT5A-induced melanoma cell migration and invasion has not yet been studied.…”

Section: Introductionmentioning

confidence: 99%

WNT5A-Induced Activation of the Protein Kinase C Substrate MARCKS Is Required for Melanoma Cell Invasion

Mohapatra

Yadav

Toftdahl

et al. 2020

Cancers

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WNT5A is a well-known mediator of melanoma cell invasion and metastasis via its ability to activate protein kinase C (PKC), which is monitored by phosphorylation of the endogenous PKC substrate myristoylated alanine-rich c-kinase substrate (MARCKS). However, a possible direct contribution of MARCKS in WNT5A-mediated melanoma cell invasion has not been investigated. Analyses of melanoma patient databases suggested that similar to WNT5A expression, MARCKS expression appears to be associated with increased metastasis. A relationship between the two is suggested by the findings that recombinant WNT5A (rWNT5A) induces both increased expression and phosphorylation of MARCKS, whereas WNT5A silencing does the opposite. Moreover, WNT5A-induced invasion of melanoma cells was blocked by siRNA targeting MARCKS, indicating a crucial role of MARCKS expression and/or its phosphorylation. Next, we employed a peptide inhibitor of MARCKS phosphorylation that did not affect MARCKS expression and found that it abolished WNT5A-induced melanoma cell invasion. Similarly, rWNT5A induced the accumulation of phosphorylated MARCKS in membrane protrusions at the leading edge of melanoma cells. Our results demonstrate that WNT5A-induced phosphorylation of MARCKS is not only an indicator of PKC activity but also a crucial regulator of the metastatic behavior of melanoma and therefore an attractive future antimetastatic target in melanoma patients.

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A multi-omics approach to elucidate okadaic acid-induced changes in human HepaRG hepatocarcinoma cells

Wuerger,

Sprenger,

Krasikova

et al. 2024

Arch Toxicol

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Okadaic acid (OA), a prevalent marine biotoxin found in shellfish, is known for causing acute gastrointestinal symptoms. Despite its potential to reach the bloodstream and the liver, the hepatic effects of OA are not well understood, highlighting a significant research gap. This study aims to comprehensively elucidate the impact of OA on the liver by examining the transcriptome, proteome, and phosphoproteome alterations in human HepaRG liver cells exposed to non-cytotoxic OA concentrations. We employed an integrative multi-omics approach, encompassing RNA sequencing, shotgun proteomics, phosphoproteomics, and targeted DigiWest analysis. This enabled a detailed exploration of gene and protein expression changes, alongside phosphorylation patterns under OA treatment. The study reveals concentration- and time-dependent deregulation in gene and protein expression, with a significant down-regulation of xenobiotic and lipid metabolism pathways. Up-regulated pathways include actin crosslink formation and a deregulation of apoptotic pathways. Notably, our results revealed that OA, as a potent phosphatase inhibitor, induces alterations in actin filament organization. Phosphoproteomics data highlighted the importance of phosphorylation in enzyme activity regulation, particularly affecting proteins involved in the regulation of the cytoskeleton. OA's inhibition of PP2A further leads to various downstream effects, including alterations in protein translation and energy metabolism. This research expands the understanding of OA's systemic impact, emphasizing its role in modulating the phosphorylation landscape, which influences crucial cellular processes. The results underscore OA's multifaceted effects on the liver, particularly through PP2A inhibition, impacting xenobiotic metabolism, cytoskeletal dynamics, and energy homeostasis. These insights enhance our comprehension of OA's biological significance and potential health risks.

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Myristoylated alanine-rich C kinase substrate (MARCKS): a multirole signaling protein in cancers

Cited by 54 publications

References 86 publications

Involvement of dual‐strand of the miR‐144 duplex and their targets in the pathogenesis of lung squamous cell carcinoma

Involvement of dual‐strand of the miR‐144 duplex and their targets in the pathogenesis of lung squamous cell carcinoma

WNT5A-Induced Activation of the Protein Kinase C Substrate MARCKS Is Required for Melanoma Cell Invasion

A multi-omics approach to elucidate okadaic acid-induced changes in human HepaRG hepatocarcinoma cells

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