Pitx1, also known as pituitary homeobox 1 gene, is a key regulator in animal growth and development [2]. It participates in multiple biological processes, such as cell growth, development, progression and invasion in various malignant tumors [1]. In embryonic mouse hindlimbs, Pitx1 promotes chondrogenesis and myogenesis by directly regulating several key members of the cartilage and muscle transcriptional networks, like Sox9 and Six1 [5].

In cancer research, in osteosarcoma, elevated Pitx1 suppresses cell proliferation and migration, associated with the FAK/Src and PI3k/Akt signaling pathways [3]. In gastric cancer, overexpression of Pitx1 increases the sensitivity of cancer cells to 5-fluorouracil and cisplatin, while knockdown decreases the sensitivity, and lower expression of Pitx1 in Asian patients is associated with a poor prognosis [6]. In melanoma, overexpression of Pitx1 reduces cell proliferation and increases apoptosis, regulating the transcription of SOX family genes [4]. In breast cancer, increased Pitx1 expression correlates with worse relapse-free survival, disease-specific survival, and overall survival, and is positively correlated with metastatic relapse-free survival and distant metastasis-free survival [1].

In conclusion, Pitx1 is crucial in animal growth and development, especially in limb and skeletal system development. In disease conditions, particularly in various cancers, Pitx1 plays diverse roles in tumor progression, metastasis, and chemotherapeutic sensitivity, as revealed by functional studies in different cell lines and patient-based bioinformatics analysis. Understanding Pitx1's functions provides insights into cancer mechanisms and potential therapeutic targets.