Overexpression of MARCKS indicates a poor prognosis of oral squamous cell carcinoma

Li, Chengjing; Xia, Rong; Xue, Haowei; Hu, Yukun; Sun, Ming; Fang, Dongdong; Yang, Wenyu; Xiao, Feng; Hou, Jun

doi:10.3892/ol.2018.9311

Cited by 4 publications

(3 citation statements)

References 27 publications

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“…The sFRP protein family consists of Wnt negative regulators that either bind directly to the Wnt proteins and prevent them from binding to their receptors, or bind Wnt receptors to prevent the formation of Wnt-receptor complexes [17]. In the study by Li et al [43] (2015), SFRP4 expression was found to be significantly elevated in carcinoma tissues compared to normal cervical tissues and was found to be upregulated in HPV (+) oropharyngeal tissue samples [44]. To the best of our knowledge, this is the first study investigating the presence of sFRP4 in cervicovaginal smears of HPV (+) and HPV (−) patients.…”

Section: Discussion/conclusionmentioning

confidence: 99%

Impact of Human Papillomavirus on Wnt/Beta-Catenin Signaling in Morphological Inconspicuous Cervicovaginal Cells

et al. 2022

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Introduction: The aim of this study was to identify early changes in the Wnt/beta-catenin signaling pathway in high-risk human papillomavirus (HPV) infected cervicovaginal cells and to correlate these changes with cell proliferation, apoptosis, and autophagic processes. Methods: We evaluated 91 cervicovaginal smears of women with (n = 41) and without (n = 50) HPV-DNA. Smears were stained against beta-catenin, c-myc, secreted frizzled-related protein 4 (sFRP4), cleaved caspase-3, and the autophagy markers Beclin-1 and light chain 3B. In addition, sFRP-1, -2, -3, -4, -5 mRNA levels were determined by quantitative reverse transcription-PCR in primary keratinocytes and FaDu cells expressing HPV16-E6, -E7, or -E6E7. Results: Our data indicated that the Wnt/beta-catenin signaling is activated in HPV (+) cervicovaginal cells that can already be detected in cells with no obvious changes in cellular morphology (HPV [+]/cyto [−]). These cells also had significantly higher sFRP4 levels when compared to HPV-negative samples. In primary keratinocytes, sFRP4 was found to be absent and sFRP1 and sFRP2 to be repressed in the presence of HPV16-E6 and E7. Interestingly, sFRP4 is expressed in FaDu cells and can be upregulated in the presence of E6E7. Curiously, SFRP4 expression correlated with an increase in the level of autophagic markers in HPV (+)/cyto (−) smears. Conclusion: In conclusion, the activation of the Wnt/beta-catenin signaling pathway and upregulation of sFRP4, paralleled by an activation of the autophagic pathway may represent predisposing cellular factors early after HPV infection which need to be further determined in larger study.

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Section: Discussion/conclusionmentioning

confidence: 99%

Impact of Human Papillomavirus on Wnt/Beta-Catenin Signaling in Morphological Inconspicuous Cervicovaginal Cells

et al. 2022

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“…A growing body of evidence implicates the myristoylated alanine-rich C-kinase substrate (MARCKS), and the highly homologous MARCKS-like protein 1 (MARCKSL1) in cancer migration and metastasis. Both MARCKS and MAR-CKSL1 are activated by phosphorylation, suggesting that MARCKS-targeted therapies could be used to treat cancer metastasis [6][7][8][9][10][11][12][13]. Our understanding of the molecular mechanisms underlying the role of MARCKS in promoting cancer metastasis and therapeutic resistance is still incomplete; however, much progress has been made [14,15].…”

Section: Introductionmentioning

confidence: 99%

The Role of MARCKS in Metastasis and Treatment Resistance of Solid Tumors

Chiu

Zhao

Chen

et al. 2022

Cancers

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The myristoylated alanine-rich C-kinase substrate (MARCKS) is a membrane-associated protein kinase C (PKC) substrate ubiquitously expressed in eukaryotic cells. MARCKS plays important roles in multiple cellular processes, including cell adhesion and motility, mucin secretion, exocytosis, and inflammatory response. Aberrant MARCKS signaling has been observed in the development and progression of multiple cancer types. In addition, MARCKS facilitates cancer metastasis through modulating cancer cell migration and invasion. Moreover, MARCKS contributes to treatment resistance, likely by promoting cancer stem cell renewal as well as immunosuppression. In this review, we describe MARCKS protein structure, cellular localization, and biological functions. We then discuss the role of MARCKS in cancer metastasis as well as its mechanisms of action in solid tumors. Finally, we review recent advances in targeting MARCKS as a new therapeutic strategy in cancer management.

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“…MARCKS, traditionally a PKC substrate, is a well-conserved protein frequently expressed in various tissues and implicated in several different cellular processes [ 22 ]. Studies have revealed that increased tumor cell expression of MARCKS is associated with poor prognosis in several cancer types [ 23 , 24 , 25 ]. MARCKS is a dynamic molecule that constantly shuttles between the plasma membrane and the cytosol depending on its phosphorylation status.…”

Section: Introductionmentioning

confidence: 99%

Increased MARCKS Activity in BRAF Inhibitor-Resistant Melanoma Cells Is Essential for Their Enhanced Metastatic Behavior Independent of Elevated WNT5A and IL-6 Signaling

Yadav

Jobe

Satapathy

et al. 2022

Cancers

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Treatment of melanoma with a BRAF inhibitor (BRAFi) frequently initiates development of BRAFi resistance, leading to increased tumor progression and metastasis. Previously, we showed that combined inhibition of elevated WNT5A and IL-6 signaling reduced the invasion and migration of BRAFi-resistant (BRAFi-R) melanoma cells. However, the use of a combined approach per se and the need for high inhibitor concentrations to achieve this effect indicate a need for an alternative and single target. One such target could be myristoylated alanine-rich C-kinase substrate (MARCKS), a downstream target of WNT5A in BRAFi-sensitive melanoma cells. Our results revealed that MARCKS protein expression and activity are significantly elevated in PLX4032 and PLX4720 BRAFi-R A375 and HTB63 melanoma cells. Surprisingly, neither WNT5A nor IL-6 contributed to the increases in MARCKS expression and activity in BRAFi-R melanoma cells, unlike in BRAFi-sensitive melanoma cells. However, despite the above findings, our functional validation experiments revealed that MARCKS is essential for the increased metastatic behavior of BRAFi-R melanoma cells. Knockdown of MARCKS in BRAFi-R melanoma cells caused reductions in the F-actin content and the number of filopodia-like protrusions, explaining the impaired migration, invasion and metastasis of these cells observed in vitro and in an in vivo zebrafish model. In our search for an alternative explanation for the increased activity of MARCKS in BRAFi-R melanoma cells, we found elevated basal activities of PKCα, PKCε, PKCι, and RhoA. Interestingly, combined inhibition of basal PKC and RhoA effectively impaired MARCKS activity in BRAFi-R melanoma cells. Our results reveal that MARCKS is an attractive single antimetastatic target in BRAFi-R melanoma cells.

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Overexpression of MARCKS indicates a poor prognosis of oral squamous cell carcinoma

Cited by 4 publications

References 27 publications

Impact of Human Papillomavirus on Wnt/Beta-Catenin Signaling in Morphological Inconspicuous Cervicovaginal Cells

Impact of Human Papillomavirus on Wnt/Beta-Catenin Signaling in Morphological Inconspicuous Cervicovaginal Cells

The Role of MARCKS in Metastasis and Treatment Resistance of Solid Tumors

Increased MARCKS Activity in BRAF Inhibitor-Resistant Melanoma Cells Is Essential for Their Enhanced Metastatic Behavior Independent of Elevated WNT5A and IL-6 Signaling

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