LACTB, a Metabolic Therapeutic Target in Clinical Cancer Application

Abstract

Serine beta-lactamase-like protein (LACTB) is the only mammalian mitochondrial homolog evolved from penicillin-binding proteins and β-lactamases (PBP-βLs) in bacteria. LACTB, an active-site serine protease, polymerizes into stable filaments, which are localized to the intermembrane space (IMS) of mitochondrion and involved in the submitochondrial organization, modulating mitochondrial lipid metabolism. Cancer pathogenesis and progression are relevant to the alterations in mitochondrial metabolism. Metabolic reprogramming contributes to cancer cell behavior. This article (1) evidences the clinical implications of LACTB on neoplastic cell proliferation and migration and tumor growth and metastasis as well as LACTB’s involvement in chemotherapeutic and immunotherapeutic responses; (2) sketches the structural basis for LACTB activity and function; and (3) highlights the relevant regulatory mechanisms to LACTB. The abnormal expression of LACTB has been associated with clinicopathological features of cancer tissues and outcomes of anticancer therapies. With the current pioneer researches on the tumor-suppressed function, structural basis, and regulatory mechanism of LACTB, the perspective hints at a great appeal of enzymic property, polymerization, mutation, and epigenetic and post-translational modifications in investigating LACTB’s role in cancer pathogenesis. This perspective provides novel insights for LACTB as a metabolic regulator with potential to develop targeted cancer therapies or neoadjuvant therapeutic interventions.