Genetic tricks to track melanoma heterogeneity DOI Creative Commons
Christian Mosimann

Disease Models & Mechanisms, Journal Year: 2022, Volume and Issue: 15(9)

Published: Sept. 1, 2022

Melanoma is a malignant tumor that arises from pigment-producing cells in the skin, melanocytes. With ultraviolet radiation sun or skin-tanning equipment as major triggers, melanoma global health concern. Although early diagnosis supports successful treatment, advanced tumors harbor mix of different cell populations show variable resistance to treatment such chemotherapy. The mechanisms underlying this remain unclear, part because longitudinal animal models have been challenging establish.Travnickova et al. now decoded new tumor-supporting features mixed occurring by harnessing genetic tools zebrafish, pioneering model study melanoma. authors combined two tricks available zebrafish. First, they used unique temperature-sensitive mutation gene mitfa encodes protein necessary for formation, which enabled interruption pigment maturation shifting zebrafish slightly higher temperature. Second, applied transgene-based labeling with cre/loxP system irreversibly mark prior expression fluorescently glowing proteins. combination these techniques (1) kill off depend on function survive, and (2) watch then grow back when were switched standard water temperature.After having validated approach several experimental angles, established rare, so-called ‘persister cells’ are original survive function. These persister fueled growth reminiscent relapse after patients. Importantly, although do not require survival nonetheless activate critical gene.Together, overcame significant technical challenges gain insights into contributing melanoma, underscoring power uncover basic disease mechanisms. results underline plasticity individual importance targeting molecular processes efficiently counter relapse. authors' enable deeper characterization tumors, opening path comparative studies human aim discovering therapeutic targets.

Language: Английский

Cancer drug-tolerant persister cells: from biological questions to clinical opportunities DOI
Mariangela Russo,

Mengnuo Chen,

Elisa Mariella

et al.

Nature reviews. Cancer, Journal Year: 2024, Volume and Issue: 24(10), P. 694 - 717

Published: Sept. 2, 2024

Language: Английский

Citations

17
Melanocyte lineage dynamics in development, growth and disease DOI Creative Commons
Alessandro Brombin, E. Elizabeth Patton

Development, Journal Year: 2024, Volume and Issue: 151(15)

Published: Aug. 1, 2024

Melanocytes evolved to produce the melanin that gives colour our hair, eyes and skin. The melanocyte lineage also rise melanoma, most lethal form of skin cancer. differentiates from neural crest cells during development, melanocytes reside in where they are replenished by stem cells. Because molecular mechanisms necessary for specification, migration, proliferation differentiation co-opted melanoma initiation progression, studying development is directly relevant human disease. Here, through lens advances cellular omic genomic technologies, we review latest findings differentiation, how these developmental pathways become dysregulated

Language: Английский

Citations

8
ALDH1A3-acetaldehyde metabolism potentiates transcriptional heterogeneity in melanoma DOI Creative Commons
Yuting Lu, Jana Trávníčková, Mihaly Badonyi

et al.

Cell Reports, Journal Year: 2024, Volume and Issue: 43(7), P. 114406 - 114406

Published: July 1, 2024

Language: Английский

Citations

5
Long-term non-invasive drug treatments in adult zebrafish that lead to melanoma drug resistance DOI Creative Commons
Yuting Lu, E. Elizabeth Patton

Disease Models & Mechanisms, Journal Year: 2022, Volume and Issue: 15(5)

Published: April 8, 2022

Zebrafish embryos are widely used for drug discovery, however, administering drugs to adult zebrafish is limited by current protocols that can cause stress. Here, we developed a formulation and administration method producing food-based pellets consumed voluntarily. We applied this with BRAF-mutant melanoma, model has significantly advanced our understanding of melanoma progression, but not resistance due the limitations treatment methods. melanomas responded short-term, precise daily dosing made BRAFV600E inhibitor, vemurafenib. On-target efficacy was determined phospho-Erk staining. Continued led emergence, first time in zebrafish, acquired relapse, modelling responses seen patients. This presents controlled, non-invasive approach permits long-term studies be models.

Language: Английский

Citations

17
Development of a Triple-Negative Breast Cancer Leptomeningeal Disease Model in Zebrafish DOI Creative Commons
Udhayakumar Gopal,

Jerry D. Monroe,

Amarnath S. Marudamuthu

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(7), P. 995 - 995

Published: March 24, 2023

Leptomeningeal disease occurs when cancer cells migrate into the ventricles of brain and spinal cord then colonize meninges central nervous system. The triple-negative subtype breast often progresses toward leptomeningeal has a poor prognosis because limited treatment options. This is due, in part, to lack animal models with which study disease. Here, we developed translucent zebrafish

Language: Английский

Citations

8
Review: The Key Factors to Melanomagenesis DOI Creative Commons

Cristina-Raluca Mihulecea,

Maria Rotaru

Life, Journal Year: 2023, Volume and Issue: 13(1), P. 181 - 181

Published: Jan. 8, 2023

Melanoma is the most dangerous form of skin cancer that develops from malignant transformation melanocytes located in basal layer epidermis (cutaneous melanoma). Melanocytes may also be found meninges, eyes, ears, gastrointestinal tract, genito-urinary system, or other mucosal surfaces (mucosal caused by an uncontrolled proliferation melanocytes, at first a benign lesion (nevogenesis), but time, it transition to melanoma, determining what named, melanomagenesis. Some tumors appear spontaneously (de novo melanoma) on preexisting lesions (nevus-associated The exact cause melanoma not fully understood yet, there are some factors initiate and promote this process. This study aims provide summary latest articles regarding key lead secondary objectives reveal relationship between nevi understand “de novo” “nevus-associated melanoma” highlight differences these subtypes.

Language: Английский

Citations

7
Adult zebrafish as advanced models of human disease DOI Creative Commons
Richard M. White, E. Elizabeth Patton

Disease Models & Mechanisms, Journal Year: 2023, Volume and Issue: 16(8)

Published: July 31, 2023

ABSTRACT Modelling adult diseases to understand their aetiology and progression, develop new therapies, is a major challenge for medical biology. We are excited by efforts in the zebrafish community models of that range from cancer heart, infectious age-related diseases, those relate toxicology complex social behaviours. Here, we discuss some advances field disease, where see opportunities challenges ahead.

Language: Английский

Citations

6
Sharing resources to advance translational research DOI Creative Commons
Kirsty M. Hooper, Julija Hmeljak

Disease Models & Mechanisms, Journal Year: 2022, Volume and Issue: 15(10)

Published: Oct. 1, 2022

ABSTRACT The publication of Resource articles is essential for the dissemination novel, or substantially enhanced, tools, techniques, disease models, datasets and resources. By sharing knowledge resources in a globally accessible manner, we can support human research to accelerate translation fundamental discoveries effective treatments diagnostics diverse patient populations. To promote encourage excellence articles, Disease Models & Mechanisms (DMM) launching new ‘Outstanding Paper Prize’. celebrate this, highlight recent outstanding DMM that have ultimate goal benefitting health.

Language: Английский

Citations

3
ALDH1A3-acetaldehyde re-wires neural crest stem cell and high metabolism states to potentiate melanoma heterogeneity DOI Creative Commons
Yuting Lu, Jana Trávníčková, Mihaly Badonyi

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 1, 2023

Abstract Cancer cellular heterogeneity and therapy resistance arise substantially from metabolic transcriptional adaptations, but how these are interconnected is poorly understood. Here, we show that in melanoma, the cancer stem cell marker aldehyde dehydrogenase 1A3 (ALDH1A3) forms an enzymatic partnership with acetyl-CoA synthetase 2 (ACSS2) nucleus to couple high glucose flux acetyl-histone H3 modification of neural crest lineage metabolism genes. Importantly, acetaldehyde a metabolite source for ALDH1A3, dependent manner providing physiologic function this highly volatile toxic metabolite. In zebrafish model melanoma residual disease, subpopulation ALDH1-high cells emerges following BRAF inhibitor treatment targeting ALDH1 suicide inhibitor, nifuroxazide, delays or prevents drug-resistant relapse. Our work reveals ALDH1A3-ACSS2 directly coordinates nuclear acetaldehyde-acetyl-CoA specific chromatin-based gene regulation represents potential therapeutic vulnerability melanoma. Highlights ALDH1A3-high melanomas dual state. Nuclear ALDH1A3 partners ACSS2 promote selective H3. Acetaldehyde acetyl histone acetylation. master regulator pharmaceutical target heterogeneity.

Language: Английский

Citations

0
Genetic tricks to track melanoma heterogeneity DOI Creative Commons
Christian Mosimann

Disease Models & Mechanisms, Journal Year: 2022, Volume and Issue: 15(9)

Published: Sept. 1, 2022

Melanoma is a malignant tumor that arises from pigment-producing cells in the skin, melanocytes. With ultraviolet radiation sun or skin-tanning equipment as major triggers, melanoma global health concern. Although early diagnosis supports successful treatment, advanced tumors harbor mix of different cell populations show variable resistance to treatment such chemotherapy. The mechanisms underlying this remain unclear, part because longitudinal animal models have been challenging establish.Travnickova et al. now decoded new tumor-supporting features mixed occurring by harnessing genetic tools zebrafish, pioneering model study melanoma. authors combined two tricks available zebrafish. First, they used unique temperature-sensitive mutation gene mitfa encodes protein necessary for formation, which enabled interruption pigment maturation shifting zebrafish slightly higher temperature. Second, applied transgene-based labeling with cre/loxP system irreversibly mark prior expression fluorescently glowing proteins. combination these techniques (1) kill off depend on function survive, and (2) watch then grow back when were switched standard water temperature.After having validated approach several experimental angles, established rare, so-called ‘persister cells’ are original survive function. These persister fueled growth reminiscent relapse after patients. Importantly, although do not require survival nonetheless activate critical gene.Together, overcame significant technical challenges gain insights into contributing melanoma, underscoring power uncover basic disease mechanisms. results underline plasticity individual importance targeting molecular processes efficiently counter relapse. authors' enable deeper characterization tumors, opening path comparative studies human aim discovering therapeutic targets.

Language: Английский

Citations

0