The mammalian Sterile 20-like kinase 4 (MST4) signaling in tumor progression: Implications for therapy. (1st June 2023) - Getu, Ayechew A.
Abstract: Cancer is a leading cause of death in humans, with a complex and dynamic nature that makes it challenging to fully comprehend and treat. The Mammalian Sterile 20-Like Kinase 4 (MST4 or STK26) is a serine/threonine-protein kinase that plays a crucial role in cell migration and polarity in both normal and tumor cells via activation of intracellular signaling molecules and pathways. MST4 is involved in tumor cell proliferation, migration and invasion, epithelial-mesenchymal transition (EMT), survival, and cancer metastasis through modulation of downstream signaling pathways including the extracellular signal-regulated kinase (ERK) and protein kinase B (AKT) pathways. Additionally, MST4 interacts with programmed cell death 10 (PDCD10) to promote tumor proliferation and migration. MST4 phosphorylates autophagy related 4B cysteine peptidase (ATG4B) to mediate autophagy signaling, promote tumor cell survival and proliferation, and contribute to treatment resistance. Taken together, MST4 functions as an oncogene and is a promising therapeutic target which deserves further exploration. Graphical abstract: Image 1 Highlights: MST4, a serine/threonine-protein kinase, plays a crucial role in regulating cell migration and polarity in normal and tumor cells. MST4 modulates ERK and AKT signaling pathways to facilitate tumor cell proliferation, migration, invasion, EMT, survival, and metastasis. MST4 phosphorylates ATG4B to mediate autophagy signaling, promote tumor cell survival, proliferation, and drug resistance. Recent findings suggest this molecule is an oncogene and a promising therapeutic target, warranting further exploration.