Reciprocal regulation of MelCAM and AKT in human melanoma

Li, Gang; Kalabis, Jiří; Xu, Xiaowei; Meier, Friedegund; Oka, Masahiro; Bogenrieder, Thomas; Herlyn, Meenhard

doi:10.1038/sj.onc.1206819

Cited by 76 publications

(81 citation statements)

References 58 publications

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“…MelCAM has a reciprocal regulation loop with the serine/threonine kinase, AKT. Inhibition of elevated AKT activity in human melanoma cell lines substantially reduced the expression of MelCAM; conversely, overexpression of constitutively active AKT up-regulated the levels of MelCAM [117]. In addition, overexpression of MelCAM in melanoma cells activated endogenous AKT and inhibited the proapoptotic protein BAD, leading to increased survival under stress conditions.…”

Section: Melcammentioning

confidence: 97%

Melanocyte Receptors: Clinical Implications and Therapeutic Relevance

Carlson

Linette

Aplin

et al. 2007

Dermatologic Clinics

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Melanocytes are an intraepidermal population of dendritic cells responsible for the production of melanin, a pigment that varies from yellow to brown to black pigment that after transfer to neighboring keratinocytes acts both as an endogenous screen and a buffering system against harmful ultraviolet (UV) wavelengths in sunlight [1]. Skin pigmentation has both individual and societal implications. The cosmetic desire for increased pigmentation (tanning) has resulted in many deleterious alterations including hastened skin ageing with wrinkles and poikiloderma and an increase in lentigines, melanocytic nevi, and melanoma. Focal or widespread loss of normal pigmentation not only renders individuals extraordinarily vulnerable to the harmful effects of sunlight (eg, increased risk of skin cancer in albinism), but it can also result in severe emotional stress and, in some societies, ostracism and discrimination (eg, vitiligo).Melanocytes are derived from the neural crest and are located along the basal layer of the epidermis and within the hair follicle, predominately the basal layer of the hair bulb matrix [1,2]. By the 50th day of intrauterine life, melanocytes can be detected in the epidermis; their migration to the epidermis and survival is dependent on receptor tyrosine kinase (RTK) c-Kit and its ligand stem cell factor (SCF) within the epidermis [3,4]. Mutations of the c-Kit gene lead to patches of hypopigmentation caused by lack of melanocyte migration, termed piebaldism [5]. Another important signaling molecule in melanocyte migration and development is Wnt5a, which signals via the Frizzled-5 receptor [6]. Overexpression of Wnt5a/ Frizzled is found in melanomas and associated with increased cell motility and invasiveness [7,8].Skin keratinocytes obtain melanin pigment from melanocytes, and keratinocytes provide the necessary microenvironment for melanocyte survival, proliferation, differentiation, and migration via production of ligands that interact with melanocyte receptors [1,[9][10][11] NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript epidermal melanin unit denotes the symbiotic relationship between one melanocyte transporting melanin via its dendritic processes to approximately 36 keratinocytes [10]. Melanocytes are located on the basement membrane among basal keratinocytes at ratio of 1 melanocyte per 5 basal keratinocytes in hematoxylin and eosin-stained histologic sections. This balance is maintained through regulated induction of melanocyte division. During childhood as the skin surface expands, throughout adulthood to maintain melanocyte numbers, and in response to exposure to sunlight or skin wounding, melanocytes are stimulated to proliferate at a low rate. Melanocyte proliferation entails uncoupling from keratinocytes, loss of their dendrites, cell division, migration along the basement membrane, then recoupling with keratinocytes to form the epidermal melanin unit. Keratinocytes regulate melanocyte growth and expression of melanocyte cell surface receptors via cell adhes...

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Section: Melcammentioning

confidence: 97%

Melanocyte Receptors: Clinical Implications and Therapeutic Relevance

Carlson

Linette

Aplin

et al. 2007

Dermatologic Clinics

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“…Human melanoma cell lines WM35, SBcl2, LU1205 (also known as 1205lu), WM9, WM793 [18,21,41,42] and OM431 were maintained in DMEM medium supplemented with 10% fetal bovine serum, L-glutamine and antibiotics. FEMX, HHMSX and LOX, human melanoma lines [43] were maintained in RPMI1640 medium supplemented with 10% FCS and antibiotics.…”

Section: Cell Linesmentioning

confidence: 99%

Dual treatment with COX-2 inhibitor and sodium arsenite leads to induction of surface Fas Ligand expression and Fas-Ligand-mediated apoptosis in human melanoma cells

Ivanov¹,

Hei²

2006

Experimental Cell Research

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Most human melanomas express Fas receptor on the cell surface, and treatment with exogenous Fas Ligand (FasL) efficiently induces apoptosis of these cells. In contrast, endogenous surface expression of FasL is suppressed in Fas-positive melanomas. We report here the use of a combination of sodium arsenite, an inhibitor of NF-κB activation, and NS398, a cyclooxygenase-2 (COX-2) inhibitor, for restoration of the surface FasL expression. We observed a large increase of Fas-mediated apoptosis in Fas-positive melanomas. This was due to induction of FasL surface expression and increased susceptibility to Fas death signaling after arsenite and NS398 treatment. Furthermore, silencing COX-2 expression by specific RNAi also effectively increased surface FasL expression following arsenite treatment. Upregulation of the surface FasL levels was based on an increase in the efficiency of translocation to the cell surface and stabilization of FasL protein on the cell surface, rather than on acceleration of the FasL gene transcription. Data obtained demonstrate that the combination of arsenite with inhibitors of COX-2 may affect the target cancer cells via induction of FasL-mediated death signaling.

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“…Overexpression of β3 integrin in melanoma cells leads to highly increased invasiveness and tumorigenicity [40]. Signaling through the αvβ3 receptor in melanoma cells occurs through the MAPK proliferation pathway, whereas signaling for the other major adhesion receptor, MCAM or CD146, occurs through the survival AKT pathway [41]. Thus, adhesion receptors cooperate with receptor tyrosine kinases for activation of the major proliferation and survival pathways [42].…”

Section: Progression: the E-cadherin To N-cadherin Switchmentioning

confidence: 99%

Recent Advances in Melanoma Biology

Perlis

Herlyn

2004

The Oncologist

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The incidence and mortality rates of melanoma have increased at annual rates of 2%-3% for the last 30 years. Disseminated disease is largely refractory to cytotoxic chemotherapy and is almost universally fatal. Several recent advances in melanoma biology offer new strategies for potentially treating this aggressive malignancy. This review focuses on three significant advances involving tumor initiation, etiology, and progression. New experimental models reveal a direct role for UV-B light in initiating melanomas in human skin. Studies on E-and N-cadherin elucidate the importance of local homeostatic mechanisms in regulating tumor progression. Finally, several discoveries concerning apoptotic mechanisms in melanoma suggest strategies for future treatments.

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Reciprocal regulation of MelCAM and AKT in human melanoma

Cited by 76 publications

References 58 publications

Melanocyte Receptors: Clinical Implications and Therapeutic Relevance

Melanocyte Receptors: Clinical Implications and Therapeutic Relevance

Dual treatment with COX-2 inhibitor and sodium arsenite leads to induction of surface Fas Ligand expression and Fas-Ligand-mediated apoptosis in human melanoma cells

Recent Advances in Melanoma Biology

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