Palladin, an actin-associated protein, is required for adherens junction formation and intercellular adhesion in HCT116 colorectal cancer cells.
Palladin is a scaffold protein involved in the formation of actin-associated protein complexes. Gene expression array analysis on the poorly metastatic HCT116 colon cancer cell line and a metastatic derivative cell line (E1) with EMT (epithelial-mesenchymal transition) features showed a down-regulation of palladin gene expression in the latter. Knockdown of palladin expression in the HCT116 cells suppressed junctional localization of E-cadherin, reduced intercellular adhesion and collective cell migration, showing that palladin plays an important role in maintaining the integrity of adherens junctions. The acquisition of the EMT features by the E1 cell line was dependent on the Erk pathway. Inhibition of this pathway by U0126 treatment in E1 cells resulted in the re-expression of palladin, relocalization of E-cadherin to the adherens junctions and a reversal of EMT features. The re-establishment of intercellular adhesion was dependent on palladin expression. The down-regulation of palladin was also observed in poorly-differentiated tumor tubules and dissociated tumor cells that have undergone de-differentiation in human primary colon tumors. Our data show that palladin is an integral component of adherens junctions and plays a role in the localization of E-cadherin to the junctions. The loss of palladin may be an integral part of EMT, an early step in the metastatic spread of colon carcinoma.
Tay
Puei Nam
PN
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Tan
Patrick
P
Lan
Yuhong
Y
Leung
Carol Ho-Wing
CH
Laban
Mirtha
M
Tan
Tze Chin
TC
Ni
Hongmin
H
Manikandan
Jayapal
J
Rashid
Suhaimi Bin Abdul
SB
Yan
Benedict
B
Yap
Celestial Therese
CT
Lim
Lina Hsiu Kim
LH
Lim
Yaw Chyn
YC
Hooi
Shing Chuan
SC
D022005:Adherens Junctions / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D015703:Antigens, CD; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D054337:Cell Dedifferentiation; D002465:Cell Movement / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034622:RNA Interference; D013160:Splenic Neoplasms / Q000378:metabolism / Q000556:secondary; D013997:Time Factors; D014162:Transfection
D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; C412722:PALLD protein, human; D010750:Phosphoproteins; D047428:Protein Kinase Inhibitors; D048049:Extracellular Signal-Regulated MAP Kinases