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resistance in cancer cells as shown in SGC7901/ADR gastric cancer cells or MCF-7/

ADR breast cancer cells [ 24 , 25 ]. Besides cancer cell lines, PrP has been reported

to be upregulated in many types of cancers (Table 13.1). Together, these results sug-

gest that PrP participates into many important aspects of tumorigenesis.

In this review, we will focus on physiological functions of PrP implied in cancer

cell migration and growth and dissect how these functions contribute to

tumorigenesis.

13.2 PrP Participates in Cell Adhesion and Migration

Most cancer patients die due to cancer cell metastasis which includes cell adhesion

and migration. The role of PrP playing in cell adhesion and migration might be

conserved evolutionary. Unlike mammalian PrP which only composed of one PrP

gene, zebra fish has two PrP genes named PrP1 and PrP2. PrP-downregulated zebra

fish embryo showed arrested gastrulation due to deficient morphogenetic cell move-

ments [ 26 ]. In addition, using morpholino knockdown and PrP2-targeted inactiva-

tion, [ 27 ] found rosette formation defects in PrP2 morphants, which suggests an

abnormal primordium organization and a loss of cell adhesion during migration of

the primordium. Such a defect is accompanied by mislocation of adherens junction

proteins, E-cadherin and ß-catenin. In a systematic integrin adhesome profiling

study, PrP is one of the molecules in consensus adhesion [ 28 ]. This is also supported

by other studies. In a large-scale quantitative and comparative interactome investi-

gation, Watts et al. identified a physical association between PrP and ß1 integrins in

mouse neuroblastoma N2a cells [ 29 ]. In addition, we showed in melanoma cell line

A7 that PrP existed in the functional protein complex with FLNa and ß1 integrins,

of which the binding between pro-PrP and FLNa enhanced the association between

FLNa and ß1 integrins, thus promoting cell adhesion and migration [ 30 ]. The above

observation is consistent with the fact that PrP is located at the outer cellular

Table 13.1 Reported tumors with PrP family protein expression

Prion or prion-like protein Cancer type References

PrP Gastric cancer [ 90 – 94 ]

PrP Breast cancer [ 10 , 42 , 70 ]

Pro-PrP Pancreatic cancer [ 46 ]

Pro-PrP Melanoma [ 30 ]

PrP Glioblastoma [ 95 , 96 ]

PrP and Dpl Osteosarcoma [ 97 ]

PrP and Dpl Colon cancer [ 89 , 98 , 99 ]

Dpl Lung cancer [ 89 ]

PrP Head and neck squamous cell

carcinoma

[ 100 ]

PrP Oral squamous cells carcinoma [ 87 ]

X. Yang et al.