Pbx3-KO Mouse

Pbx3, a homeodomain-containing transcription factor of the pre-B cell leukemia (PBX) family, has unique features like forming specific and stable DNA interactions without co-factors. It is extensively involved in early development and some adult processes, and plays crucial roles in cancer-related biological processes [1].

In a murine acute myeloid leukemia (AML) model, Pbx3 was found to be up-regulated by ATP-P2X1-mediated signaling, and it transactivated BCAT1 to maintain the fates of leukemia-initiating cells (LICs). P2X1 knockdown, which decreased Pbx3 levels, inhibited the proliferation of human AML cell lines and primary cells [2].

In colorectal cancer, Pbx3 promoted the pentose phosphate pathway (PPP) by enhancing G6PD expression, thus promoting tumorigenesis both in vitro and in vivo [3].

In glioma, Pbx3 was highly expressed and its expression increased with malignancy. It was an independent influencing factor for poor prognosis of low-grade glioma (LGG) patients and had potential value for early diagnosis and prognosis prediction [4].

In triple-negative breast cancer (TNBC), Pbx3 activated DLG1-AS1, which then promoted TNBC cell proliferation, invasion, and migration by sponging miR-16-5p [5].

In gastric cancer, PBX3 interacted with the SNHG10 promoter to activate its expression, and SNHG10 maintained PBX3 mRNA stability through recruiting DDX54, facilitating cell growth [6].

In breast cancer, leptin activated PBX3 expression in a STAT3-dependent manner, and PBX3 conferred letrozole resistance via transactivation of the FGFR1 signaling [7].

In papillary thyroid carcinoma (PTC), high levels of PBX3 were correlated with tumor size, lymphatic metastasis, TMN stage, and poor prognosis. Overexpression of PBX3 promoted cell proliferation, while its knockdown induced cell cycle arrest, and inhibited angiogenesis and tumor growth in vitro and in vivo [8].

In conclusion, Pbx3 is a multifunctional gene involved in multiple biological processes, especially in cancer development and progression. Studies using various in vivo models, such as mouse models of AML, have revealed its role in promoting cancer cell survival, proliferation, and drug resistance, making it a potential therapeutic target in multiple cancer types.