Caveolin-1 expression in hyperproliferative skin disorders: A potential predictive marker of disease severity and progression

Gheida, Shereen F.; Neinaa, Yomna Mazid El‐Hamd; Mohammed, Dareen A.

doi:10.1016/j.dsi.2018.06.002

Cited by 7 publications

(17 citation statements)

References 22 publications

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“…Dysregulation of Cav1 expression in the human skin is associated with hyperproliferative diseases such as melanoma and non-melanoma cancers but also psoriasis (Carè et al, 2011; Gheida et al, 2018; Kruglikov and Scherer, 2019). In melanoma, Cav1 function remains very controversial, since it is recognized as a tumor suppressor and an oncogene (Felicetti et al, 2009; Trimmer et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Caveolae coupling of melanocytes signaling and mechanics is required for human skin pigmentation

Domingues

Hurbain

Gilles-Marsens

et al. 2019

Preprint

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22Tissue homeostasis requires regulation of cell-cell communication, which relies on signaling 23 molecules and cell contacts. In skin epidermis, keratinocytes secrete specific factors transduced 24 by melanocytes into signaling cues to promote their pigmentation and dendrite outgrowth, while 25 melanocytes transfer melanin pigments to keratinocytes to convey skin photoprotection. How 26 epidermal cells integrate these functions remains poorly characterized. Here, we found that 27 caveolae polarize in melanocytes and are particularly abundant at melanocyte-keratinocyte 28 interface. Caveolae in melanocytes are sensitive to ultra-violet radiations and miRNAs released 29 by keratinocytes. Preventing caveolae formation in melanocytes results in increased production 30 of intracellular cAMP and melanin pigments, but decreases cell protrusions, cell-cell contacts, 31 pigment transfer and epidermis pigmentation. Altogether, our data establish that, in 32 melanocytes, caveolae serve as key molecular hubs that couple signaling outputs from 33 keratinocytes to mechanical plasticity. This process is crucial to maintain cell-cell contacts and 34 intercellular communication, skin pigmentation and tissue homeostasis. 84Epidermal melanocytes and keratinocytes are in constant communication, not only via secreted 85 factors and exosomes that modulate cellular responses, but also by the physical contacts they 86 establish to maintain the tissue homeostasis and pigmentation. Here, we report a new function 87 for caveolae, which, by integrating the biochemical and mechanical behavior of melanocytes, 88 control melanin transfer to keratinocytes and epidermis pigmentation. Altogether, this study 89 provides the first evidence for a physiologic role of caveolae as a molecular sensing platform 90 required for the homeostasis of the largest human tissue, the skin epidermis. 91 5 Results 92 Caveolae polarize in melanocytes and are positively-regulated by keratinocytes-secreted 93 factors 94Melanocytes and keratinocytes establish a complex intercellular dialogue required for skin 95 photoprotection. 2D-co-culture systems, where these two cell types share the same medium, 96have been widely used to study intercellular communication and pigment transfer between 97 epidermal cells (Hirobe, 2005; Lei et al., 2002). To evaluate the distribution of caveolae within 98 the epidermal unit in 2D, normal human melanocytes and keratinocytes were co-cultured and 99 labelled for the two constituents of caveolae, Cav1 or Cavin1. Immunofluorescence microscopy 100 revealed that both Cav1 and Cavin1, and therefore caveolae, were asymmetrically distributed in 101 melanocytes (Figures 1A and B), which were identified by the abundant staining of the 102 premelanosome protein PMEL [hereafter referred as melanin, see Experimental Procedures; 103 (Raposo et al., 2001)]. This polarization was not observed in keratinocytes.104 Cells can break their symmetry in response to local external chemical and/or mechanical cues 105 such as signaling molecules and/or cell-ce...

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Section: Discussionmentioning

confidence: 99%

Caveolae coupling of melanocytes signaling and mechanics is required for human skin pigmentation

Domingues

Hurbain

Gilles-Marsens

et al. 2019

Preprint

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show abstract

“…One study compared immunohistochemical expression of Cav1 in patients with cutaneous SCC with normal control skin specimens and observed a statistically significant downregulation of Cav1 expression in SCCs compared to the control group, in both intensity and pattern of expression. [157] Furthermore, poorly differentiated SCCs showed significantly reduced Cav1 expression compared to moderately and well-differentiated SCCs, suggesting that Cav1 downregulation not only plays a role in the promotion of SCC tumorigenesis, but also in its progression. The study went on to explore the potential role of Cav1 in the pathogenesis on non-melanoma skin cancers (NMSCs) and ultimately found that levels of Cav1 expression could be used as predictive biomarkers for patients at risk of cancer progression.…”

Section: Cav1 In Cutaneous Squamous Cell Carcinomas (Sccs)mentioning

confidence: 93%

“…The study went on to explore the potential role of Cav1 in the pathogenesis on non-melanoma skin cancers (NMSCs) and ultimately found that levels of Cav1 expression could be used as predictive biomarkers for patients at risk of cancer progression. [157] Murine models of cutaneous SCC demonstrate similar relationship between Cav1 and tumor development, where mice overexpressing Cav1 exhibit decreased in vitro cell proliferation, as well as decreased in vivo tumor incidence, volume and weight. [158] Conversely, Cav1-null mice exhibit increased cell and tumor growth, in addition to increased invasive ability and incidence of spontaneous lymph node metastasis, which is likely due to hyperactivation of the MAPK pathway in the Cav1-null mice, [158] thus introducing…”

Section: Cav1 In Cutaneous Squamous Cell Carcinomas (Sccs)mentioning

confidence: 94%

“…For example, its expression is associated not only with cancer suppression in oesophageal adenocarcinoma, lung adenocarcinoma, and ovarian cancer, but also with progression of prostate cancer, renal cell carcinoma, and lung squamous cell carcinoma. [154][155][156] This argues for a cell-specific role where Cav1 can [157] In vitro In vivo…”

Section: Role Of C Aveolin S In S K In C Ancersmentioning

confidence: 99%

“…Although the association between Cav1-BCC development has been largely unexplored, a recent study correlated Cav1 expression with the clinicopathological parameters of BCCs. [157] BCC samples dem-…”

Section: Cav1 In Basal Cell Carcinoma (Bccs)mentioning

confidence: 99%

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The importance of caveolins and caveolae to dermatology: Lessons from the caves and beyond

Egger

Rajabi‐Estarabadi

Williams

et al. 2020

Experimental Dermatology

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Caveolae are flask‐shaped invaginations of the cell membrane rich in cholesterol and sphingomyelin, with caveolin proteins acting as their primary structural components that allow compartmentalization and orchestration of various signalling molecules. In this review, we discuss how pleiotropic functions of caveolin‐1 (Cav1) and its intricate roles in numerous cellular functions including lipid trafficking, signalling, cell migration and proliferation, as well as cellular senescence, infection and inflammation, are integral for normal development and functioning of skin and its appendages. We then examine how disruption of the homeostatic levels of Cav1 can lead to development of various cutaneous pathophysiologies including skin cancers, cutaneous fibroses, psoriasis, alopecia, age‐related changes in skin and aberrant wound healing and propose how levels of Cav1 may have theragnostic value in skin physiology/pathophysiology.

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Caveolin-1 in skin aging – From innocent bystander to major contributor

Kruglikov¹,

Zhang

Scherer

2019

Ageing Research Reviews

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Caveolin-1 expression in hyperproliferative skin disorders: A potential predictive marker of disease severity and progression

Cited by 7 publications

References 22 publications

Caveolae coupling of melanocytes signaling and mechanics is required for human skin pigmentation

Caveolae coupling of melanocytes signaling and mechanics is required for human skin pigmentation

The importance of caveolins and caveolae to dermatology: Lessons from the caves and beyond

Caveolin-1 in skin aging – From innocent bystander to major contributor

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