Clic3-flox Mouse

CLIC3, chloride intracellular channel 3, belongs to the glutathione-S-transferase (GSTs) superfamily. It regulates chloride ion concentration, cell membrane potential, trans-epithelial transport, cell volume, and apoptotic processes [6]. It is involved in diverse biological pathways such as the cell cycle, focal adhesion, extracellular matrix (ECM) receptor interaction, and the P53 signaling pathway [3].

In cancer research, CLIC3 has been extensively studied. In bladder cancer, it promotes cell proliferation by interacting with NAT10 to inhibit N4-acetylcytidine modification of p21 mRNA, leading to reduced p21 expression [1]. High CLIC3 mRNA expression in bladder cancer is associated with poor prognosis and is related to adverse clinicopathological factors [3]. In breast cancer, it controls the recycling of late endosomal MT1-MMP, dictating invasion and metastasis in estrogen receptor-negative breast cancer cells [5]. In pancreatic ductal adenocarcinoma, CLIC3, along with Rab25, promotes integrin recycling from late endosomes/lysosomes, and its expression predicts lymph node metastasis and poor prognosis [9]. In gastric cancer, it functions as a Cl-channel in the plasma membrane, and decreased expression is associated with unfavorable prognosis [4]. In salivary gland mucoepidermoid carcinoma, hypomethylation of the CLIC3 promoter leads to its overexpression [10]. Secreted CLIC3 from cancer-associated fibroblasts promotes angiogenesis and cancer cell invasiveness through its glutathione-dependent oxidoreductase activity [2].

In summary, CLIC3 plays crucial roles in cancer progression, being involved in processes like cell proliferation, invasion, and metastasis across multiple cancer types. Additionally, it may have a role in abnormal placental function in pregnancy disorders such as fetal growth restriction and pre-eclampsia [6], and is identified as an immune-related hub gene in schizophrenia, potentially serving as a diagnostic biomarker and therapeutic target [7]. Recently, it has been shown to mediate fibroblast cellular senescence by interacting with ERK7 [8].