GABPA, also known as GA-binding protein transcription factor subunit alpha, is a transcription factor broadly involved in physiological and pathological processes. It has been implicated in pathways related to cell proliferation, migration, invasion, and ferroptosis, and is of great biological importance in tumorigenesis [3,2]. Genetic models, such as gene knockout (KO) or conditional knockout (CKO) mouse models, could potentially be valuable for further exploring its functions.

In multiple cancer types, GABPA shows down-regulation. In gastric cancer, its low expression predicts high incidences of lymphatic and distant metastasis, and overexpression blocks cell migration by targeting GPX1 [1]. In clear cell renal cell carcinoma, GABPA is downregulated in cancer tissues, and its overexpression suppresses cell proliferation, migration, invasion, and increases susceptibility to ferroptosis by promoting ACSL4-mediated ferroptosis [2]. In endometrial carcinoma, low GABPA expression is an independent poor prognostic factor, and its mRNA expression is negatively correlated with methylation level [3]. In renal cell carcinoma, GABPA acts as a tumor suppressor by stimulating TGFBR2 expression and TGFβ signaling, while the oncometabolite L-2-HG epigenetically inhibits GABPA expression to drive cancer aggressiveness [4]. In follicular thyroid tumours, GABPA directly regulates DICER1, acting as a tumour suppressor [5]. In papillary thyroid carcinoma, GABPA inhibits invasion/metastasis by regulating DICER1 expression and is negatively associated with TERT expression and promoter mutations [6]. In bladder cancer, GABPA dictates luminal identity and inhibits aggressive diseases by promoting cellular differentiation despite its stimulatory effect on telomerase/TERT activation [7]. In hepatocellular carcinoma, GABPA inhibits cell migration by modulating E-cadherin and is downregulated, correlating with poor prognosis [8].

In conclusion, GABPA appears to function as a tumor suppressor in multiple cancer types. Its down-regulation is often associated with poor prognosis, aggressive phenotypes, and metastasis. Studies, potentially including those using KO/CKO mouse models in the future, can further clarify its role in these disease processes, which may provide new therapeutic strategies for cancer treatment.