Significance of Midkine Signaling in Women’s Cancers: Novel Biomarker and Therapeutic Target
Emily J. Aller, Hareesh B. Nair, Ratna K. Vadlamudi, Suryavathi Viswanadhapalli
Abstract
Midkine (MDK) is a multifunctional protein that is secreted into the extracellular space. It functions as a cytokine or growth factor, modulating a variety of signaling pathways implicated in angiogenesis, antitumor immunity, metastasis, and therapy resistance. MDK overexpression has been documented in a variety of cancers, including those that affect women. MDK mediates its effects through activation of key signaling pathways such as MAPK/ERK, PI3K/AKT, and STAT3, which are pivotal for cell cycle progression, survival, and maintenance of stemness. Obesity and estrogen signaling, a known critical driver of women's cancer, further elevate the levels of MDK. MDK's effects are mediated by a variety of membrane receptors, such as integrins, protein tyrosine phosphatase ζ (PTPζ), anaplastic lymphoma kinase (ALK), and neurogenic locus notch homolog protein 2 (Notch2). Recently published studies have indicated that MDK is a potential therapeutic target and a biomarker for the progression of women's cancer. In this review, we have provided a concise summary of the most recent papers that have examined the potential biomarker and therapeutic utility of MDK signaling in women's cancer.