The CD44 Receptor Interacts with P-Glycoprotein to Promote Cell Migration and Invasion in Cancer

• Published in: Cancer research (Chicago, Ill.) Vol. 65; no. 15; pp. 6660 - 6667
• Main Authors: Miletti-González, Karl E., Chen, Shiling, Muthukumaran, Neelakandan, Saglimbeni, Giuseppa N., Wu, Xiaohua, Yang, Jinming, Apolito, Kevin, Shih, Weichung J., Hait, William N., Rodríguez-Rodríguez, Lorna
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.08.2005
• Subjects: ATP-Binding Cassette, Sub-Family B, Member 1 - antagonists & inhibitors; ATP-Binding Cassette, Sub-Family B, Member 1 - biosynthesis; ATP-Binding Cassette, Sub-Family B, Member 1 - genetics; ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism; Biological and medical sciences; Cell Line, Tumor; Cell Membrane - metabolism; Cell Movement - drug effects; Cell Movement - physiology; Dissemination; Drug Resistance, Neoplasm; Female; Flupenthixol - pharmacology; Humans; Hyaluronan Receptors - biosynthesis; Hyaluronan Receptors - genetics; Hyaluronan Receptors - metabolism; Immunoprecipitation; Medical sciences; Neoplasm Invasiveness; Neoplasms - drug therapy; Neoplasms - metabolism; Neoplasms - pathology; RNA Interference; Transfection; Tumor cell; Tumors; Antineoplastic agent; Cell motility; Phenotype; Multiple resistance; P Glycoprotein; Metastasis; Malignant tumor; Invasion; Cell migration; Biological receptor
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.CAN-04-3478

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.