Most early-stage ccRCC is easy to be ignored since it has no clinical symptoms, and most patients are detected through physical examination. However, most patients, who presented with symptoms were in advanced stage or had lung, bone, brain metastasis. Oftenly they are unable to benefit from available treatment options. To further improve the efficacy of patients with ccRCC, especially those with advanced metastasis, there is an urgent need to discover new therapeutic targets and develop new anticancer drugs.

Metabolic reprogramming of cancer is one of its core malignant characteristics, involved in the occurrence and development of cancer. In some cases, reprogrammed metabolic activity can be used for diagnosis, detection, and treatment [1]. Metabolic requirements evolve throughout tumor progression. The early stages of tumor growth require nutrient absorption and biosynthesis, and additional subtype-selective metabolic requirements occur in locally invasive cancers. Tumors acquire dependence on new pathways at later stages particularly for metastasis and treatment resistance [2]. Metabolic reprogramming has been extensively studied in ccRCC [3].

PSAT1 is a member of the V-class pyridoxal-phosphate-dependent aminotransferase family. The serine synthesis pathway (SSP) is mainly divided into three steps. PSAT1, the key enzyme in this synthesis pathway，converts 3 PHP to phosphoglycine in a transamination reaction that uses glutamate-derived nitrogen and produces α-ketoglutarate (α-KG) [4]. It has been reported to play an important role in tumorigenesis and malignant progression in multiple cancers, including non-small cell lung cancer (NSCLC), breast cancer, gastric cancer, colon cancer, and ovarian cancer [[5], [6], [7], [8], [9]]. However, its role and clinical significance in ccRCC remain poorly understood.

Here, we found that PSAT1 is differential expressed between ccRCC and adjacent normal tissues, and is closely associated with advanced tumor grade，metastasis and adverse outcomes. Knockdown of PSAT1 reduces proliferation, motility and drug resistance of ccRCC. PSAT1 regulates the growth of renal cancer cells by affecting the cell cycle and apoptosis. It promotes the motility of ccRCC by influencing focal adhesion and extracellular matrix composition. Rap1, TGF-β and Aplein pathways are activated to facilitate the malignant progression. Generally, these suggest that PSAT1 is a prognostic marker for ccRCC，which may serve as a new target to improve patient clinical outcomes.