The Links between Parkinson's Disease and Cancer

Abstract

Epidemiologic studies indicate a decreased incidence of most cancer types in Parkinson's disease (PD) patients. However, some neoplasms are associated with a higher risk of occurrence in PD patients. Both pathologies share some common biological pathways. Although the etiologies of PD and cancer are multifactorial, some factors associated with PD, such as α-synuclein aggregation; mutations of PINK1, PARKIN, and DJ-1; mitochondrial dysfunction; and oxidative stress can also be involved in cancer proliferation or cancer suppression. The main protein associated with PD, i.e., α-synuclein, can be involved in some types of neoplastic formations. On the other hand, however, its downregulation has been found in the other cancers. PINK1 can act as oncogenic or a tumor suppressor. PARKIN dysfunction may lead to some cancers' growth, and its expression may be associated with some tumors' suppression. DJ-1 mutation is involved in PD pathogenesis, but its increased expression was found in some neoplasms, such as melanoma or breast, lung, colorectal, uterine, hepatocellular, and nasopharyngeal cancers. Both mitochondrial dysfunction and oxidative stress are involved in PD and cancer development. The aim of this review is to summarize the possible associations between PD and carcinogenesis.

Keywords: DJ-1; PARK; PINK; Parkinson’s disease; cancer; mitophagy; mutations; oxidative stress; α-synuclein.

Figure 1

PINK1/PARKIN pathway activation in polarized mitochondria. Depolarization of mitochondria/mitochondrial damage activates PARKIN-dependent mitophagy by induction of PINK-1 kinase in the outer mitochondrial membrane (OMM). Loss of membrane potential necessary for component replacement is responsible for increased concentration of PINK1 in the OMM. PINK1 stabilizes and phosphorylates Parkin, which, when activated, is responsible for ubiquitinylation of proteins on mitochondrial surface, which is a signal for proteasomes to degrade the mitochondrion. In polarized mitochondria, PINK1 is continuously being imported into the mitochondrial intermembrane space, where it is degraded by PARL proteases. Low levels of PINK1 prevent mitophagy of healthy mitochondria.

Figure 2

Schematic drawing of possible association between Parkinson’s disease and cancer.