Evolution and functions of stanniocalcins in cancer

Abstract

Corpuscles of stannius (CS), a small endocrine gland located on the ventral surface of the kidneys of bony fishes, is extracted to purify stanniocalcins (STCs), which inhibit whole-body Ca2+ influx in the whole body, especially in gill and gut. CSs were first considered to be unique endocrine glands in fish, but were further verified to appear in mammalians, indicating that STCs may function in mammalians as calcium regulation, oxidative stress, anti-inflammation, angiogenesis, ischemia reperfusion, etc. Moreover, the relationship and molecular mechanisms of STC1 expression in cancer become the studied focus and front field. STC2 as a STC1 homolog is identified by searching for related sequences in expressed sequence tag databases. Although mammalian STC1 and STC2 are not expressed ubiquitously in tissue cells, they are distributed in a wide variety of tissues and organs including cancer, and play an important role in tumor development and progression. Molecular structureSTC is present in all vertebrates as two isoforms, STC1 and STC2, encoded by separate genes. 1 STC1, originally described as an antihypercalcemic hormone in fish, is highly expressed in differentiated mammalian neurons. STC1 adopts a dimeric and slightly elongated structure with a high content of alpha-helices. 2 STC2, a homolog of STC1, is a 56kD glycoprotein hormone that confers calcitonin-like activity. A widespread distribution of SCT1 and STC2 is present in mammals and fish, in which the highest amount of STC mRNA is in the heart but lower amounts are found in the neural complex, branchial basket, and endostyle. STCs have a conserved pattern of 10 cysteines in Evolution and functions of stanniocalcins in cancer S-J Chu, 1 J Zhang, 2 R Zhang, 2 W-W Lu 2 and J-S Zhu 2 Abstract Stanniocalcin (STC), first isolated from the corpuscles of stannius of teleost fishes, was originally known for its regulation on calcium/phosphate transport. Increasing evidence demonstrates that STCs display the important function in some physiological and pathological behaviors such as calcium regulation, oxidative stress, anti-inflammation, angiogenesis, ischemia reperfusion, nerve diseases, etc. Moreover, STCs are implicated in the development and progression of multiple malignancies through promoting cell growth, proliferation, invasion, metastasis, and apoptotic escape. Some studies have shown that NF-κB upregulates STC expression, thereby activating the downstream HIF-1/ERK1/2 signaling pathway, enhancing the transcriptional activity of tumor-related factors (MMP-2/9, cyclinD1, Bcl-2, N-cadherin, etc) and contributing to tumorigenesis. Here, this brief review describes recent progress of STCs in mammalians, focused mainly on their critical functions in cancer.

Stanniocalcin-2 contributes to mesenchymal stromal cells attenuating murine contact hypersensitivity mainly via reducing CD8+ Tc1 cells

“…The stanniocalcin (STC) family consists of two proteins, STC1 and STC2, which are expressed in various human tissues 16 , such as pancreas, spleen, kidney, and skeletal muscle. Numerous studies have examined STC1 and STC2 in the tumor microenvironment, where they have positive effects on tumor migration and invasion 17 , 18 . Clinically, STC2 has been proposed to be a biomarker for various cancers, in association with the formation of tumor neovascularization 19 , 20 .…”

Prognostic Significance of STC2 and DNA methylation in Head and Neck Squamous Cell Carcinoma: A Study Based on the TCGA and GEO Databases

“…Numerous studies of STC2 expression within the tumor microenvironment found that STC2 enhanced tumor cell migration and invasion [42,43]. Clinical studies con rmed STC2 as a new biomarker of multiple cancers due to its involvement in tumor neovascularization [44,45].…”

Butyl octyl phthalate interacts with estrogen receptor α in MCF‑7 breast cancer cells to promote cancer development

“…Finally, the glycoprotein STC2 was overexpressed as well. The glycoprotein is involved in the homeostasis of calcium and phosphate (57). STC2 has been reported to be upregulated in E2-treated MCF-7 cells (58), breast cancer (59) and is associated with proliferation in cancer (60,61).…”