title: Prolactin-Induced Protein regulates cell adhesion in breast cancer.
abstract: Prolactin-Induced Prolactin (PIP) is widely expressed in breast cancer and has key cellular functions in this disease that include promoting invasion and cell cycle progression. Notably, we have recently identified a strong association between PIP-binding partners and a number of cell functions that are involved in cell adhesion. Therefore in this study, we investigated the effect of PIP on the regulation of cell adhesion using PIP-silencing in breast cancer cell lines T-47D, BT-474, and MFM-223. Our findings suggest that PIP expression is necessary for cell adhesion in a process that shows variation in the pattern of PIP regulation of cell-matrix and cell-cell adhesions based on the types of adhesion surface and breast cancer cell line. In this respect, we observed that PIP-silencing markedly reduced cell adhesion to uncoated plates in all three cell lines. In addition, in T-47D and MFM-223 cells fibronectin matrix induced baseline adhesion and reversed the PIP-silencing mediated reduction of cell adhesion. However, in BT-474 cells we did not observe an induction of baseline adhesion by fibronectin and PIP-silencing led to a marked reduction in cell adhesion to both uncoated and fibronectin-coated plates. Furthermore, we observed a significant reduction in cell-cell adhesion of BT-474 cell line following PIP-silencing. To explain an underlying mechanism for PIP regulation of cell adhesion, we found that PIP expression is necessary for the formation of α-actinin/actin-rich podosomes at the adhesion-sites of breast cancer cells. In summary, this study suggests that PIP expression regulates the process of cell adhesion in breast cancer.
authors.affiliation: Holden Comprehensive Cancer Center, University of Iowa, Medical Education and Research Facility, 375 Newton Road, Iowa City, IA 52242, USA.
authors.forename: Marion
authors.initials: M
authors.lastname: Vanneste
authors.affiliation: Holden Comprehensive Cancer Center, University of Iowa, Medical Education and Research Facility, 375 Newton Road, Iowa City, IA 52242, USA. Electronic address: a.naderi1996@gmail.com.
authors.forename: Ali
authors.initials: A
authors.lastname: Naderi
mesh_terms: D001943:Breast Neoplasms / Q000473:pathology / Q000503:physiopathology*; D002352:Carrier Proteins / Q000378:metabolism*; D002448:Cell Adhesion; D002450:Cell Communication; D045744:Cell Line, Tumor; D022001:Focal Adhesions; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D026901:Membrane Transport Proteins; D000069261:Podosomes / Q000378:metabolism* / Q000473:pathology
chemical_list: D002352:Carrier Proteins; D006023:Glycoproteins; D026901:Membrane Transport Proteins; C488892:PIP protein, human
keywords: Breast cancer; Cell adhesion; Prolactin-Induced Protein