Spin1, also known as Spindlin1, is a histone methylation reader. It epigenetically controls multiple tumorigenesis-associated signaling pathways like the Wnt, PI3K/AKT, and RET pathways, and is thus of great importance in cancer-related biological processes [1]. It is a transcriptional co-activator with functions in embryonic development and emerging roles in cancer [2].

Functionally, Spin1 depletion inhibits cell proliferation, migration, invasion, and decreases the clonogenic capacity, impairs double-strand break repair, and increases radiosensitivity in non-small cell lung cancer (NSCLC), revealing its role in NSCLC progression and radioresistance [3]. In liver cancer, Spin1 modulates abnormal lipid metabolism by up-regulating FASN and co-activating SREBP1c, enhancing tumor growth [4]. In human seminoma, Spin1 overexpression reduces apoptosis and up-regulates CYCD1, indicating its pro-oncogenic role [5]. In gastric cancer, Spin1 promotes cell proliferation, migration, invasion, and cell cycle progression via the MDM2-p21-E2F1 signaling pathway, and forms a positive feedback loop with E2F1 [6]. Also, Spin1 ablation activates p53, suppresses cell growth, reduces clonogenic ability, and induces apoptosis of human cancer cells by blocking the uL18-MDM2-p53 pathway [7].

In conclusion, Spin1 is a crucial factor in multiple biological and disease-related processes, especially in cancer. Its functions in promoting tumorigenesis, chemoresistance, and radioresistance are revealed through various loss-of-function experiments, highlighting its potential as a therapeutic target for cancers such as NSCLC, liver cancer, seminoma, and gastric cancer.