Insight into dipeptidase 1: structure, function, and mechanism in gastrointestinal cancer diseases

Dipeptidase 1 (DPEP1), initially identified as a renal membrane enzyme in mature human kidneys, plays a pivotal role in various cellular processes. It facilitates the exchange of materials and signal transduction across cell membranes, contributing significantly to dipeptide hydrolysis, glucose and lipid metabolism, immune inflammation, and ferroptosis, among other cellular functions. Extensive research has delineated the complex role of DPEP1 in oncogenesis and tumor progression, with its influence being context dependent. DPEP1 has been observed to promote oncogenic activities in hepatocellular carcinoma, non-small cell lung cancer, colorectal cancer, and lymphoblastic malignancies and is hypothesized to participate in multiple biological processes, including tumor cell invasion, metastatic spread, cellular signaling pathways, cell-matrix interactions, and evasion of immune surveillance. Conversely, DPEP1 has been identified as a tumor suppressor in pancreatic adenocarcinoma, lobular breast carcinoma, and Wilms tumor. Moreover, the role of DPEP1 in colorectal cancer has been increasingly recognized in recent research. Emerging evidence suggests that DPEP1 substantially augments the metastatic and invasive potential of colorectal cancer cells, facilitates immune evasion, and confers resistance to chemotherapeutic agents. Despite these findings, the precise molecular mechanisms remain to be fully characterized. This systematic review endeavors to elucidate the structural and functional attributes of the DPEP1 protein, with the aim to clarify its regulatory mechanisms and assess its clinical relevance in oncology. Gaining a thorough understanding of the physiological role and molecular underpinnings of DPEP1 is critical to informing the diagnostic, therapeutic, and prognostic paradigms of related pathologies. It is anticipated that these insights will facilitate the discovery of novel therapeutic targets and generate new investigative trajectories, particularly in the clinical management of colorectal cancer.