FAM3B

What is FAM3B protein?

FAM3B (FAM3 metabolism regulating signaling molecule B) gene is a protein coding gene which situated on the long arm of chromosome 21 at locus 21q22. FAM3B, also known as PANDER (Pancreatic DERived factor), is a protein that is part of the FAM3 (Family with Sequence Similarity 3) gene family. It is a secreted signaling molecule involved in various biological processes, particularly in glucose metabolism and the pathogenesis of type 2 diabetes. FAM3B is expressed in several tissues, including the pancreas, and has been identified as a ligand for the fibroblast growth factor receptor (FGFR), playing a role in developmental processes. FAM3B has been shown to promote gluconeogenesis and lipogenesis in hepatocytes, which means it can increase the production of glucose and fat in liver cells. The FAM3B protein is consisted of 235 amino acids and its molecular mass is approximately 26.0 kDa.

What is the function of FAM3B protein?

FAM3B is expressed in several tissues, including the pancreas, and it has been shown to promote gluconeogenesis and lipogenesis in hepatocytes, which means it can increase the production of glucose and fat in liver cells. Furthermore, FAM3B has been identified as a ligand for fibroblast growth factor receptor (FGFR), indicating its role in developmental processes and potentially in cancer progression. It can also function as a co-activator of FOXO1, enhancing the transcriptional activity of FOXO1 on gluconeogenic genes, thereby promoting gluconeogenesis in hepatocytes.

Fig1. FAM3B mediates high glucose-induced VSMC proliferation and migration via inhibition of miR-322-5p. (Wenxiang Zhang, 2017)

FAM3B Related Signaling Pathway

FAM3B has been identified as a ligand for the fibroblast growth factor receptor (FGFR). It can activate the FGFR/ERK pathway, which is important in developmental processes and has implications in cancer progression. FAM3B functions as a co-activator of the transcription factor FOXO1, enhancing its transcriptional activity on gluconeogenic genes, thereby promoting gluconeogenesis in hepatocytes. Overexpression of FAM3B has been shown to promote the progression of esophageal carcinoma via regulation of the AKT-MDM2-p53 pathway, which is involved in cell survival and apoptosis.

FAM3B Related Diseases

FAM3B (PANDER) is associated with a variety of diseases, especially metabolic diseases and tumors. In terms of metabolic diseases, FAM3B has been linked to the development of type 2 diabetes by promoting gluconeogenesis and lipid production in the liver. In addition, the abnormal expression of FAM3B in Down syndrome may be related to the metabolic characteristics of the disease. In the field of tumor, abnormal expression of FAM3B is associated with the occurrence and development of gastric cancer, oral squamous cell carcinoma, colon cancer and other tumors. Dysfunction of FAM3B may lead to proliferation, invasion, and metastasis of tumor cells, making it a potential diagnostic and therapeutic target.

Bioapplications of FAM3B

Because of its role in disease, FAM3B is a potential therapeutic target. The biological function of FAM3B and its role in disease offer the possibility of developing new drugs, including small molecule inhibitors or antibodies that target the FAM3B signaling pathway. Among them, FAM3B antibody is widely used in lab reseaches. The expression pattern of FAM3B in some diseases may make it a biomarker for disease diagnosis, prognostic assessment, and therapeutic response monitoring.

Case Study 1: Song-Lin He, 2019

FAM3B has been suggested to play important roles in the progression of many cancers, such as gastric, oral, colon and prostate cancer. However, little is known about the role of FAM3B in human esophageal squamous cell carcinoma (ESCC). In the present study, researchers found that FAM3B expression was higher in ESCC tissues than in adjacent normal tissues. Using quantitative real-time polymerase chain reaction, they found similar results in cell lines. FAM3B expression was significantly related to T/TNM stage. Importantly, Kaplan-Meier analysis revealed that a high expression level of FAM3B predicted a poor outcome for ESCC patients. Overexpression of FAM3B inhibits ESCC cell death, increases oesophageal tumour growth in xenografted nude mice, and promotes ESCC cell migration and invasion. Further studies confirmed that FAM3B regulates the AKT-MDM2-p53 pathway and two core epithelial-to-mesenchymal transition process markers, Snail and E-cadherin.

Fig1. Up-regulation of FAM3B mRNA expressions in ESCC tissue samples.

Fig2. The protein expression level of FAM3B was examined by Western blot analysis.

Case Study 2: Zongmeng Li, 2013

FAM3B mRNA has been predicted to have multiple splicing forms. Its secretory form PANDER is decreased in gastric cancers with high invasiveness and metastasis. Here researchers found that its non-secretory form FAM3B-258 was highly expressed in most colon cancer cell lines and colorectal adenocarcinoma tissues but not hepatocellular carcinoma, lung carcinoma and pancreatic adenocarcinoma cell lines. Elevation of FAM3B-258 was associated with poor cancer cell differentiation. Stable overexpression of FAM3B-258 in colon cancer cells downregulated adhesion proteins, upregulated Slug and Cdc42, promoted cell migration and invasion in vitro and metastasis in nude mice. Slug mediated FAM3B-258-induced downregulation of adhesion molecules, upregulation of Cdc42, and invasion of colon cancer cells. The expression of FAM3B-258 in human colorectal adenocarcinomas was positively correlated with Slug.

Fig3. Overexpression of FAM3B-258 in HCT116 cells alters adhesion protein and related transcription factor expression.

Fig4. Overexpression of FAM3B-258 promotes establishment of metastases of colon cancer cells in vivo.

FAM3B has several biochemical functions, for example, cytokine activity. Some of the functions are cooperated with other proteins, some of the functions could acted by FAM3B itself. We selected most functions FAM3B had, and list some proteins which have the same functions with FAM3B. You can find most of the proteins on our site.

FAM3B 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 FAM3B here. Most of them are supplied by our site. Hope this information will be useful for your research of FAM3B.