FILIP1L, short for Filamin A-interacting protein 1-like, is a multifunctional protein. It has been implicated in multiple biological processes such as apoptosis, cell proliferation, and differentiation. It is associated with pathways like Wnt/β-catenin signaling, and its down-regulation has been linked to cancer progression, suggesting it may function as a tumor suppressor [1,2,3]. Genetic models, like knockout (KO) and conditional knockout (CKO) mouse models, have been crucial in understanding its function.

In mucinous colorectal adenocarcinoma, loss of FILIP1L in colon-specific knockout mice induced colonic epithelial hyperplasia and mucin secretion, and increased xenograft growth. This shows that FILIP1L loss drives the unique neoplastic characteristics of this aggressive subtype of cancer by causing abnormal stabilization of the centrosome-associated chaperone protein PFDN1, leading to multinucleation and cytokinesis defects [1]. In lung-specific knockout mice, reduction of FILIP1L induced lung adenoma formation and mucin secretion, enhancing lung adenocarcinoma progression through mucin production, inflammation, and fibrosis [2].

In conclusion, FILIP1L is an important protein in maintaining normal cellular functions. Studies using KO/CKO mouse models have revealed its role in suppressing the development of mucinous colorectal adenocarcinoma and lung adenocarcinoma. Understanding FILIP1L's functions provides insights into the mechanisms of cancer development and may offer potential therapeutic targets for these malignancies.

References:

1. Kwon, Mijung, Rubio, Genesaret, Nolan, Nicholas, Pine, Sharon R, Libutti, Steven K. 2021. FILIP1L Loss Is a Driver of Aggressive Mucinous Colorectal Adenocarcinoma and Mediates Cytokinesis Defects through PFDN1. In Cancer research, 81, 5523-5539. doi:10.1158/0008-5472.CAN-21-0897. https://pubmed.ncbi.nlm.nih.gov/34417201/

2. Kwon, Mijung, Rubio, Genesaret, Wang, Haitao, Pine, Sharon R, Libutti, Steven K. 2022. Smoking-associated Downregulation of FILIP1L Enhances Lung Adenocarcinoma Progression Through Mucin Production, Inflammation, and Fibrosis. In Cancer research communications, 2, 1197-1213. doi:10.1158/2767-9764.CRC-22-0233. https://pubmed.ncbi.nlm.nih.gov/36860703/

3. Kwon, Mijung, Libutti, Steven K. 2014. Filamin A interacting protein 1-like as a therapeutic target in cancer. In Expert opinion on therapeutic targets, 18, 1435-47. doi:10.1517/14728222.2014.957181. https://pubmed.ncbi.nlm.nih.gov/25200207/