S100A4

Case study 1: Yana Qi, 2022

Metastasis is the major cause of cancer-related mortalities. A tumor-supportive microenvironment, also known as the premetastatic niche at secondary tumor sites, plays a crucial role in metastasis. Remodeling of the extracellular matrix (ECM) is essential for premetastatic niche formation, especially for circulating tumor cell colonization. However, the underlying molecular mechanism that contributes to this effect remains unclear. Here, the researchers developed a lung metastasis model with 4T1 breast cancer cells and found that the metastasis critically depended on the early recruitment of macrophages to the lung. Disruption of macrophage recruitment reduced fibroblast activation and lung metastasis. Furthermore, they identified the secreted protein S100A4, which is produced by M2 macrophages and participates in fibroblast activation and ECM protein deposition via the ERK signaling pathway. Collectively, these results indicate that recruiting S100A4-expressing inflammatory macrophages plays a vital role in ECM remodeling in the premetastatic niche and may act as a potential therapeutic target for breast cancer lung metastasis.

Fig1. L929 cells were treated with rS100A4 at different concentrations, and the protein levels of α-SMA and fibronectin were assessed via western blotting.

Fig2. The migration ability of the control and rS100A4-treated groups was evaluated by Transwell assays (∗P < 0.05).

Case study 2: Anfei Liu, 2023

Lung metastasis is the leading cause of breast cancer-related death. The tumor microenvironment contributes to the metastatic colonization of tumor cells in the lungs. Tumor secretory factors are important mediators for the adaptation of cancer cells to foreign microenvironments. Here, the researchers report that tumor-secreted stanniocalcin 1 (STC1) promotes the pulmonary metastasis of breast cancer by enhancing the invasiveness of tumor cells and promoting angiogenesis and lung fibroblast activation in the metastatic microenvironment. The results show that STC1 modifies the metastatic microenvironment through its autocrine action on breast cancer cells. Specifically, STC1 upregulates the expression of S100 calcium-binding protein A4 (S100A4) by facilitating the phosphorylation of EGFR and ERK signaling in breast cancer cells. S100A4 mediates the effect of STC1 on angiogenesis and lung fibroblasts. Importantly, S100A4 knockdown diminishes STC1-induced lung metastasis of breast cancer. Moreover, activated JNK signaling upregulates STC1 expression in breast cancer cells with lung-tropism.

Fig3. Western blot analysis and the quantification of S100A4 of MDA-MB-231 cells with or without 1-h pretreatment with 100 ng/mL of rhSTC1.

Fig4. Validation of S100A4 knockdown and overexpression in human breast cancer cell lines, MDA-MB-231-STC1 and LM2-shSTC1, by Western blot analyses.

Fig1. S100A4 proteins get involved in NF-kB and AKT signaling, affecting the cell activities. (Ting Wang, 2023)

Fig2. Schematic diagram depicting the roles of STC1 in breast cancer pulmonary metastasis. (Anfei Liu, 2023)

S100A4 involved in several pathways and played different roles in them. We selected most pathways S100A4 participated on our site, such as , which may be useful for your reference. Also, other proteins which involved in the same pathway with S100A4 were listed below. Creative BioMart supplied nearly all the proteins listed, you can search them on our site.

S100A4 has several biochemical functions, for example, RAGE receptor binding, actin binding, calcium ion binding. Some of the functions are cooperated with other proteins, some of the functions could acted by S100A4 itself. We selected most functions S100A4 had, and list some proteins which have the same functions with S100A4. You can find most of the proteins on our site.

S100A4 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with S100A4 here. Most of them are supplied by our site. Hope this information will be useful for your research of S100A4.

TP53; S100B; MDM2; AREGB; BTC