Weight-bearing activity impairs nuclear membrane and genome integrity via YAP activation in plantar melanoma

Seo, Jeong Taeg; Kim, HyunSeok; Min, Kyoung Il; Kim, Changgon; Kwon, Yongsoo; Zheng, Zhenlong; Kim, Yusung; Park, Hyung‐Soon; Ju, Young Seok; Roh, Mi Ryung; Chung, Kee Yang; Kim, Joon

doi:10.1038/s41467-022-29925-x

Cited by 19 publications

(10 citation statements)

References 61 publications

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“…In plantar melanoma, continuous mechanical stress caused by weight-bearing activities activated the expression of YAP, stimulating the proliferation of melanoma cells. 75 YAP activity is also positively regulated by the ECM 76 ; ECM-mediated signaling induced by changes in cytoskeletal structure promoted tumor development through increased collagen production and remodeling, while the HU177 epitope was shown to promote melanoma cell metastasis through CDK5/YAP signaling. 77 High fibromodulin expression in the tumor microenvironment stimualted ECM remodeling, activated integrin/focal adhesion kinase pathway, and induced YAP nuclear translocation and metastatic growth and vasculogenic mimicry.…”

Section: Role Of Yap In Melanomamentioning

confidence: 99%

“…YAP is also affected by dynamic mechanical stress, which plays a role in the pathology of melanoma. In plantar melanoma, continuous mechanical stress caused by weight‐bearing activities activated the expression of YAP, stimulating the proliferation of melanoma cells 75 . YAP activity is also positively regulated by the ECM 76 ; ECM‐mediated signaling induced by changes in cytoskeletal structure promoted tumor development through increased collagen production and remodeling, while the HU177 epitope was shown to promote melanoma cell metastasis through CDK5/YAP signaling 77 .…”

Section: Relationship Between Yap and Skin Diseasesmentioning

confidence: 99%

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Recent advances in the role of Yes‐associated protein in dermatosis

Jia

Liu

2023

Skin Research and Technology

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Background: Dermatosis is a general term for diseases of the skin and skin appendages including scleroderma, psoriasis, bullous disease, atopic dermatitis, basal cell carcinoma, squamous cell carcinoma, and melanoma. These diseases affect millions of individuals globally and are a serious public health concern. However, the pathogenesis of skin diseases is not fully understood, and treatments are not optimal. Yes-associated protein (YAP) is a transcriptional coactivator that plays a role in the regulation of gene transcription and signal transduction. Aims:To study the role of Yes-associated protein in skin diseases. Materials and Methods:The present review summarizes recent advances in our understanding of the role of YAP in skin diseases, current treatments that target YAP, and potential avenues for novel therapies.Results: Abnormal YAP expression has been implicated in occurrence and development of dermatosis. YAP regulates the cell homeostasis, proliferation, differentiation, apoptosis, angiopoiesis, and epithelial-to-mesenchymal transition, among other processes. As well as, it serves as a potential target in many biological processes for treating dermatosis. Conclusions:The effects of YAP on the skin are complex and require multidimensional investigational approaches. YAP functions as an oncoprotein that can promote the occurrence and development of cancer, but there is currently limited information on the therapeutic potential of YAP inhibition for cancer treatment. Additional studies are also needed to clarify the role of YAP in the development and maturation of dermal fibroblasts; skin barrier function, homeostasis, aging, and melanin production; and dermatosis.

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Section: Role Of Yap In Melanomamentioning

confidence: 99%

Section: Relationship Between Yap and Skin Diseasesmentioning

confidence: 99%

Recent advances in the role of Yes‐associated protein in dermatosis

Jia

Liu

2023

Skin Research and Technology

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“…[7][8][9] Especially, acral melanoma occurs most commonly on weight-bearing areas of the sole, [10][11][12][13] which recent research has attributed to nuclear membrane damage resulting from mechanical stress. 14 Surgical excision of tumors at such sites results in significant distress for patients, as weight-bearing and walking are impaired. Furthermore, reconstruction of defects at such sites poses a significant challenge due to limited availability and mobility of local skin.…”

Section: Introductionmentioning

confidence: 99%

“…Compared with White patients, dark‐skinned individuals more commonly acquire melanoma on acral areas, such as the hands and feet 7–9 . Especially, acral melanoma occurs most commonly on weight‐bearing areas of the sole, 10–13 which recent research has attributed to nuclear membrane damage resulting from mechanical stress 14 . Surgical excision of tumors at such sites results in significant distress for patients, as weight‐bearing and walking are impaired.…”

Section: Introductionmentioning

confidence: 99%

Comparison of full‐thickness skin graft and punch grafting in the reconstruction of plantar defects

Lee,

Nam,

et al. 2023

The Journal of Dermatology

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Acral melanoma commonly occurs on weight‐bearing areas of the sole. Reconstruction of such areas presents a surgical challenge due to limited availability and mobility of local skin. Thus, we aimed to compare the scar outcome of full‐thickness skin graft (FTSG) and punch grafting in the reconstruction of plantar defects after melanoma surgery. We retrospectively reviewed six patients who underwent both FTSG for nonweight‐bearing areas and punch grafting for weight‐bearing areas. We compared results of FTSG and punch grafting within the same patient. Photos of completely healed scars were graded using the Stony Brook Scar Evaluation Scale (SBSES). The averages of the FTSG scores and the punch graft scores, as measured by the SBSES, were statistically compared. Punch grafting yielded a better outcome than FTSG, according to the SBSES. The average of the punch grafting scars was 4.67, which was significantly greater (p = 0.004) than that of FTSG scar scores at 1.83. For weight‐bearing areas, punch grafting should be considered as the first option of reconstruction, with FTSG as a second option for nonweight‐bearing areas. Overall, this combined approach provides an effective and safe method for reconstruction of extensive plantar wounds.

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“…For instance, the stiffness of the substrate is an important factor in manipulating phenotype specification and the proliferation of melanoma cells [ 21 ]. In addition, the invasion process and nuclear envelope integrity of melanoma are affected by mechanical compression [ 22 , 23 ]. Previously, mechanotransduction has been demonstrated as the main pathway in cell-sensing extracellular biophysical stimuli [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

Promotion of Melanoma Cell Proliferation by Cyclic Straining through Regulatory Morphogenesis

Huang

Chen

Hou

et al. 2022

IJMS

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The genotype and phenotype of acral melanoma are obviously different from UV-radiation-induced melanoma. Based on the clinical data, mechanical stimulation is believed to be a potential cause of acral melanoma. In this case, it is desirable to clarify the role of mechanical stimulation in the progression of acral melanoma. However, the pathological process of cyclic straining that stimulates acral melanoma is still unclear. In this study, the influence of cyclic straining on melanoma cell proliferation was analyzed by using a specifically designed cell culture system. In the results, cyclic straining could promote melanoma cell proliferation but was inefficient after the disruption of cytoskeleton organization. Therefore, the mechanotransduction mechanism of promoted proliferation was explored. Both myosin and actin polymerization were demonstrated to be related to cyclic straining and further influenced the morphogenesis of melanoma cells. Additionally, the activation of mechanosensing transcription factor YAP was related to regulatory morphogenesis. Furthermore, expression levels of melanoma-involved genes were regulated by cyclic straining and, finally, accelerated DNA synthesis. The results of this study will provide supplementary information for the understanding of acral melanoma.

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Weight-bearing activity impairs nuclear membrane and genome integrity via YAP activation in plantar melanoma

Cited by 19 publications

References 61 publications

Recent advances in the role of Yes‐associated protein in dermatosis

Recent advances in the role of Yes‐associated protein in dermatosis

Comparison of full‐thickness skin graft and punch grafting in the reconstruction of plantar defects

Promotion of Melanoma Cell Proliferation by Cyclic Straining through Regulatory Morphogenesis

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