Saa1-KO Mouse

SAA1, Serum amyloid A1, is a lipid-binding protein and an important regulator involved in inflammation. It is a member of the Serum Amyloid A (SAA) protein family, which are small, well-conserved proteins synthesized prominently in the liver. SAA1 contributes to high-density lipoproteins and cholesterol transport, and is also involved in tissue remodeling through metalloproteinases, and has implications in various physiological and pathological processes such as cancer metastasis, atherosclerosis, and inflammation-related disorders [4].

In pancreatic cancer, adipocytes co-cultured with cancer cells can de-differentiate into cancer-associated adipocytes (CAAs) which promote cancer cell migration, invasion, chemoresistance, and epithelial-mesenchymal transition (EMT) through SAA1 expression. Knocking down SAA1 in pancreatic cancer cells attenuated these malignant characteristics, suggesting SAA1 as a potential therapeutic target [1]. In triple-negative breast cancer, SAA1 is a regulator of adipocyte reprogramming, and its expression is associated with cancer-associated adipocyte infiltration, inflammation, and tumor aggressiveness [2]. In esophageal squamous cell carcinoma (ESCC), SAA1 promotes cancer cell proliferation, migration, and tumor growth in nude mice, and knockdown of SAA1 promotes apoptosis. SAA1 acts via β-catenin phosphorylation, and is regulated by the S1P/S1PR1 pathway [6]. In renal cancer, high SAA1 expression predicts advanced tumors, and its promoter hypomethylation leads to high expression. SAA1 may serve as a diagnostic and prognostic biomarker, and targeting it could be a novel therapeutic approach [7]. In gastric cancer-associated fibroblasts, SAA1 is upregulated possibly due to enhancer activation, and its overexpression promotes gastric cancer cell migration [8]. Also, SAA1 gene polymorphism rs10832915 is associated with an increased risk of osteoporosis in the Chinese population, and the ATT haplotype is correlated with a decreased risk [3]. SAA1 deficiency alleviates cardiac remodeling by inhibiting NF-κB/p38/JNK and TGFβ/Smad pathways in a mouse model of cardiac remodeling induced by transverse aortic banding, hindering cardiac fibrosis [5].

In summary, SAA1 is involved in inflammation, tissue remodeling, and cholesterol transport. Through gene-knockout or knockdown studies in various in vivo models, SAA1 has been shown to play significant roles in cancer progression, osteoporosis, and cardiac remodeling. These findings highlight SAA1 as a potential target for therapeutic intervention in these disease areas.

References:

1. Takehara, Masanori, Sato, Yasushi, Kimura, Tetsuo, Muguruma, Naoki, Takayama, Tetsuji. 2020. Cancer-associated adipocytes promote pancreatic cancer progression through SAA1 expression. In Cancer science, 111, 2883-2894. doi:10.1111/cas.14527. https://pubmed.ncbi.nlm.nih.gov/32535957/

2. Rybinska, Ilona, Mangano, Nunzia, Romero-Cordoba, Sandra L, Tagliabue, Elda, Triulzi, Tiziana. 2024. SAA1-dependent reprogramming of adipocytes by tumor cells is associated with triple negative breast cancer aggressiveness. In International journal of cancer, 154, 1842-1856. doi:10.1002/ijc.34859. https://pubmed.ncbi.nlm.nih.gov/38289016/

3. Zhou, Xindie, Li, Jin, Jiang, Lifeng, Huang, Yong, Xu, Nanwei. 2019. SAA1 gene polymorphisms in osteoporosis patients. In Bioscience reports, 39, . doi:10.1042/BSR20181031. https://pubmed.ncbi.nlm.nih.gov/30737305/

4. Sack, George H. . Serum Amyloid A (SAA) Proteins. In Sub-cellular biochemistry, 94, 421-436. doi:10.1007/978-3-030-41769-7_17. https://pubmed.ncbi.nlm.nih.gov/32189310/

5. Xiao, Yusha, Ni, Lihua, Shi, Hongjie, Liu, Jinping, Luo, Pengcheng. . SAA1 deficiency alleviates cardiac remodeling by inhibiting NF-κB/p38/JNK and TGFβ/Smad pathways. In FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 37, e22911. doi:10.1096/fj.202201506R. https://pubmed.ncbi.nlm.nih.gov/37022639/

6. Li, Qianqian, Tang, Maolin, Zhao, Shisheng, Ren, Ling, Hu, Weimin. 2024. SAA1 regulated by S1P/S1PR1 promotes the progression of ESCC via β-catenin activation. In Discover oncology, 15, 66. doi:10.1007/s12672-024-00923-3. https://pubmed.ncbi.nlm.nih.gov/38446289/

7. Li, Sen, Cheng, Yongbiao, Cheng, Gong, Ruan, Hailong, Zhang, Xiaoping. 2021. High SAA1 Expression Predicts Advanced Tumors in Renal Cancer. In Frontiers in oncology, 11, 649761. doi:10.3389/fonc.2021.649761. https://pubmed.ncbi.nlm.nih.gov/34084746/

8. Yasukawa, Yoshimi, Hattori, Naoko, Iida, Naoko, Seto, Yasuyuki, Ushijima, Toshikazu. . SAA1 is upregulated in gastric cancer-associated fibroblasts possibly by its enhancer activation. In Carcinogenesis, 42, 180-189. doi:10.1093/carcin/bgaa131. https://pubmed.ncbi.nlm.nih.gov/33284950/