The CD44 receptor interacts with P-glycoprotein to promote cell migration and invasion in cancer.
Invasion and metastases of cancer cells and the development of resistance to anticancer therapies are the main causes of morbidity and mortality from cancer. For more than two decades, these two important but not clearly related aspects in the biology of cancer have been extensively studied. Specifically, P-glycoprotein and CD44 have been characterized and are known to be determinants of multidrug resistance (MDR) and metastases. Despite this body of knowledge, few reports have linked the two phenotypes and only recently have there been reasons to suspect a direct connection. In this report, we show that a novel physical and genetic interaction between CD44s and P-glycoprotein is in part responsible for the correlation between MDR and invasive potential in cancer cells. P-glycoprotein-specific substrates that interfere with its function reduced in vitro invasion, migration, and the physical colocalization of CD44s and P-glycoprotein. CD44 expression in sensitive cells promoted the expression of P-glycoprotein and the MDR phenotype. RNA interference of MDR1 inhibited the rate of cell migration. These data indicate that there is a close interaction between CD44 and P-glycoprotein that results in the concurrent expression and modulation of two malignant phenotypes, invasion and MDR.
Miletti-González
Karl E
KE
Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, The Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey/Robert Wood Johnson Medical School, New Brunswick, New Jersey 08901, USA.
Chen
Shiling
S
Muthukumaran
Neelakandan
N
Saglimbeni
Giuseppa N
GN
Wu
Xiaohua
X
Yang
Jinming
J
Apolito
Kevin
K
Shih
Weichung J
WJ
Hait
William N
WN
Rodríguez-Rodríguez
Lorna
L
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D005475:Flupenthixol / Q000494:pharmacology; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D047468:Immunoprecipitation; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D034622:RNA Interference; D014162:Transfection
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018960:Hyaluronan Receptors; D005475:Flupenthixol