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What is the role of ATF4 in melanoma?

Ribosomal s6 kinase

Activating Transcription Factor 4

Lactate dehydrogenase A

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ATF4 plays a crucial role in melanoma by influencing various aspects of the disease. It has been identified that ATF4 regulates enzymes controlling amino acid metabolism, leading to resistance to LDHA inhibitors in melanoma cells . Additionally, ATF4 is involved in the MAPK/ERK pathway, where it regulates the downstream effector NLRP1, impacting metastatic melanoma cells and contributing to targeted therapy resistance . Moreover, ATF4's impact extends to the tumor microenvironment, as stromal ATF4 drives cancer-associated fibroblast functionality, tumor growth, and metastasis in melanoma and pancreatic tumors . Overall, ATF4's involvement in amino acid regulation, MAPK/ERK signaling, and stromal interactions underscores its significance in melanoma progression and treatment resistance.

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Open access•Journal Article•DOI A stromal Integrated Stress Response activates perivascular cancer-associated fibroblasts to drive angiogenesis and tumour progression Ioannis I. Verginadis, Harris Avgousti, James Monslow, Giorgos Skoufos, Frank Chinga, Kyle Kim, Nektaria Maria Leli, Ilias V. Karagounis, Brett Bell, Anastasia Velalopoulou, Carlo Salas Salinas, Victoria S. Wu, Yang Liu, Jian-lan Ye, David Scott, Andrei L. Osterman, Arjun Sengupta, Aalim M. Weljie, Meng-Chun Huang, Duo Zhang, Yi Fan, Enrico Radaelli, John W. Tobias, Florian Rambow, Jean-Christophe Marine, Xiaowei Xu, Artemis G. Hatzigeorgiou, Sandra Ryeom, J. Alan Diehl, Serge Y. Fuchs, Ellen Puré, Constantinos Koumenis - Show less +31 more 01 Jun 2022-Nature Cell Biology 22 Citations	ATF4 drives perivascular cancer-associated fibroblast activation, collagen biosynthesis, and angiogenesis in melanoma, promoting tumor progression and metastasis by supporting vascularization.
Journal Article•DOI Targeting the ATF4 pathway in cancer therapy Dean C. Singleton, Adrian L. Harris - Show less +1 more 16 Nov 2012-Expert Opinion on Therapeutic Targets 104 Citations	ATF4 in melanoma promotes cancer cell survival by regulating metabolic processes, redox balance, and angiogenesis in response to microenvironmental stresses, contributing to cancer progression and treatment resistance.
Open access•Journal Article•DOI NLRP1 Functions Downstream of the MAPK/ERK Signaling via ATF4 and Contributes to Acquired Targeted Therapy Resistance in Human Metastatic Melanoma. Zili Zhai, Prasanna K Vaddi, Jenny Mae Samson, Tomoya Takegami, Mayumi Fujita, Mayumi Fujita - Show less +5 more 30 Dec 2020-Pharmaceuticals 2 Citations	ATF4 regulates NLRP1 downstream of MAPK/ERK signaling in melanoma, impacting targeted therapy resistance. It plays a crucial role in modulating gene expression and therapeutic responses in melanoma cells.
Open access•Journal Article•DOI ATF4‐amino acid circuits: a recipe for resistance in melanoma Mario R. Fernandez, John L. Cleveland - Show less +1 more 15 Oct 2018-The EMBO Journal 3 Citations	ATF4 controls amino acid metabolism in melanoma, leading to resistance to LDHA inhibitors. It rewires metabolism, conferring resistance and suggesting potential therapeutic targets for overcoming resistance.

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