Melanocortins and the melanocortin 1 receptor, moving translationally towards melanoma prevention

Abdel‐Malek, Zalfa; Swope, Viki B.; Starner, Renny J.; Koikov, L. N.; Cassidy, Pamela B.; Leachman, Sancy A.

doi:10.1016/j.abb.2014.07.002

Cited by 52 publications

(44 citation statements)

References 125 publications

(170 reference statements)

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“…The physiological stimuli αMSH regulates melanogenesis through G s receptor MC1R by activating cAMP‐PKA‐MITF signaling axis (Levy et al , ; Videira et al , ; Abdel‐Malek et al , ). In a recent study, UV radiations were shown to induce ER Ca 2+ release through G q retinal receptor resulting in higher pigmentation levels (Bellono et al , ).…”

Section: Discussionmentioning

confidence: 99%

“…Melanin produced within melanosomes is transferred to neighboring keratinocytes, which provides protection to the skin from UV‐induced cellular damage (Natarajan et al , ). One of the major physiological determinants of pigmentation in humans is α‐melanocyte‐stimulating hormone (αMSH; Videira et al , ; Abdel‐Malek et al , ). αMSH binds to the G‐coupled receptor melanocortin‐1 receptor (MC1R) and activates melanogenesis via cAMP‐PKA‐microphthalmia transcription factor (MITF) signaling axis (Levy et al , ).…”

Section: Introductionmentioning

confidence: 99%

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STIM 1 activation of adenylyl cyclase 6 connects Ca ²⁺ and cAMP signaling during melanogenesis

et al. 2018

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Endoplasmic reticulum (ER)-plasma membrane (PM) junctions form functionally active microdomains that connect intracellular and extracellular environments. While the key role of these interfaces in maintenance of intracellular Ca levels has been uncovered in recent years, the functional significance of ER-PM junctions in non-excitable cells has remained unclear. Here, we show that the ER calcium sensor protein STIM1 (stromal interaction molecule 1) interacts with the plasma membrane-localized adenylyl cyclase 6 (ADCY6) to govern melanogenesis. The physiological stimulus α-melanocyte-stimulating hormone (αMSH) depletes ER Ca stores, thus recruiting STIM1 to ER-PM junctions, which in turn activates ADCY6. Using zebrafish as a model system, we further established STIM1's significance in regulating pigmentation STIM1 domain deletion studies reveal the importance of Ser/Pro-rich C-terminal region in this interaction. This mechanism of cAMP generation creates a positive feedback loop, controlling the output of the classical αMSH-cAMP-MITF axis in melanocytes. Our study thus delineates a signaling module that couples two fundamental secondary messengers to drive pigmentation. Given the central role of calcium and cAMP signaling pathways, this module may be operative during various other physiological processes and pathological conditions.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

STIM 1 activation of adenylyl cyclase 6 connects Ca ²⁺ and cAMP signaling during melanogenesis

et al. 2018

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“…α-MSH binds to and activates the melanocortin 1 receptors (MC1R) located on the plasma membrane of melanocytes 21 . There are three forms of MSH, α,β γ, which bind with different affinities to MCRs.…”

Section: Introductionmentioning

confidence: 99%

Chemoprevention agents for melanoma: A path forward into phase 3 clinical trials

Jeter

Bowles

Curiel‐Lewandrowski

et al. 2018

Cancer

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Recent progress in the treatment of advanced melanoma has led to unprecedented improvements in overall survival. As these new melanoma treatments have been developed and deployed in the clinic, much has been learned about the natural history of the disease. Now is the time to apply that knowledge towards the design and clinical evaluation of new chemoprevention agents. Melanoma chemoprevention has the potential to dramatically reduce both the morbidity and high costs associated with treating patients with metastatic disease. In this work, scientific and clinical melanoma experts from the national Melanoma Prevention Working Group comprised of National Cancer Trials Network (NCTN) participants, discuss research aimed at discovering and developing (or re-purposing) drugs and natural products for the prevention of melanoma, and propose an updated pipeline for translating the most promising agents into the clinic. The mechanism of action, pre-clinical data, epidemiological evidence and results of available clinical trials are discussed for each class of compounds. Selected keratinocyte carcinoma chemoprevention studies are also considered, and a rationale for their inclusion is presented. These data are summarized in a table that lists the type and level of evidence available for each class of agents. Also included in the discussion is an assessment of additional research necessary and likelihood that a given compound might be a suitable candidate for a Phase III clinical trial within the next 5 years.

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“…Both oxidative DNA damage and UV-induced mutation signatures have an overlapping footprint related to pyrimidine heterocycle chemistry. Future chemoprevention efforts of malignant melanoma may take advantage of such prevalent molecular features connecting mutation signature, pigmentation genetics, and cellular environment [124]. Similar to BRAF, melanoma driver genes like ras-related C3 botulinum toxin substrate 1 (RAC1, rho family, small GTP binding protein Rac1, Gene ID: 5879), serine/threonine kinase 11 (STK11, LKB1, Gene ID: 6794), or NRAS have such a distorted distribution of nucleotide transitions, since activation nucleotide transversions can favor or disfavor the UV melanoma signature.…”

Section: Melanoma Subtypes and Predominance Of Mapk-related Signalingmentioning

confidence: 99%

Precision medicine driven by cancer systems biology

Filipp

2017

Cancer Metastasis Rev

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Molecular insights from genome and systems biology are influencing how cancer is diagnosed and treated. We critically evaluate big data challenges in precision medicine. The melanoma research community has identified distinct subtypes involving chronic sun-induced damage and the mitogen-activated protein kinase driver pathway. In addition, despite low mutation burden, non-genomic mitogen-activated protein kinase melanoma drivers are found in membrane receptors, metabolism, or epigenetic signaling with the ability to bypass central mitogen-activated protein kinase molecules and activating a similar program of mitogenic effectors. Mutation hotspots, structural modeling, UV signature, and genomic as well as non-genomic mechanisms of disease initiation and progression are taken into consideration to identify resistance mutations and novel drug targets. A comprehensive precision medicine profile of a malignant melanoma patient illustrates future rational drug targeting strategies. Network analysis emphasizes an important role of epigenetic and metabolic master regulators in oncogenesis. Co-occurrence of driver mutations in signaling, metabolic, and epigenetic factors highlights how cumulative alterations of our genomes and epigenomes progressively lead to uncontrolled cell proliferation. Precision insights have the ability to identify independent molecular pathways suitable for drug targeting. Synergistic treatment combinations of orthogonal modalities including immunotherapy, mitogen-activated protein kinase inhibitors, epigenetic inhibitors, and metabolic inhibitors have the potential to overcome immune evasion, side effects, and drug resistance.

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Melanocortins and the melanocortin 1 receptor, moving translationally towards melanoma prevention

Cited by 52 publications

References 125 publications

STIM 1 activation of adenylyl cyclase 6 connects Ca ²⁺ and cAMP signaling during melanogenesis

STIM 1 activation of adenylyl cyclase 6 connects Ca ²⁺ and cAMP signaling during melanogenesis

Chemoprevention agents for melanoma: A path forward into phase 3 clinical trials

Precision medicine driven by cancer systems biology

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Melanocortins and the melanocortin 1 receptor, moving translationally towards melanoma prevention

Cited by 52 publications

References 125 publications

STIM 1 activation of adenylyl cyclase 6 connects Ca 2+ and cAMP signaling during melanogenesis

STIM 1 activation of adenylyl cyclase 6 connects Ca 2+ and cAMP signaling during melanogenesis

Chemoprevention agents for melanoma: A path forward into phase 3 clinical trials

Precision medicine driven by cancer systems biology

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STIM 1 activation of adenylyl cyclase 6 connects Ca ²⁺ and cAMP signaling during melanogenesis

STIM 1 activation of adenylyl cyclase 6 connects Ca ²⁺ and cAMP signaling during melanogenesis