DAB2IP, also known as AIP1 (ASK1 interacting protein), is a member of the Ras GTPase-activating protein family. It interacts directly with DAB2 and modulates various signal cascades related to cell proliferation, survival, apoptosis, and metastasis. It negatively controls Ras-dependent mitogenic signals and also regulates other oncogenic pathways such as TNFα/NF-κB, WNT/β-catenin, PI3K/AKT, and androgen receptor signaling [1,5,6].

In multiple types of cancer, DAB2IP is significantly down-regulated. Its reduced expression may indicate a poor prognosis. For example, in breast cancer, it inhibits glucose uptake under hypoxia by suppressing HIF-1α signals [2]. In colon cancer, it suppresses tumor malignancy by inhibiting GRP75-driven p53 ubiquitination [3]. In renal cell carcinoma, loss of DAB2IP impairs primary cilia formation [4]. In colorectal cancer, it down-regulates HSP90AA1 to inhibit malignant biological behaviors [7]. In triple-negative breast cancer, it attenuates chemoresistance by preventing β-catenin nuclear accumulation [9]. Also, in KRAS mutant colon cancer, its loss promotes tumor development by activating wild-type H-and N-RAS proteins and triggering inflammatory cascades [8].

In conclusion, DAB2IP functions as a tumor suppressor, modulating multiple signal pathways relevant to cancer development. Research using gene-knockout or conditional-knockout mouse models (although not explicitly detailed in all references but inferred from the in-vivo and loss-of-function studies) has been crucial in revealing its role in various cancer-related biological processes, highlighting its potential as a target for cancer therapies [1-10].