Palladin expression is a conserved characteristic of the desmoplastic tumor microenvironment and contributes to altered gene expression.
The stroma surrounding solid tumors contributes in complex ways to tumor progression. Cancer-associated fibroblasts (CAFs) are the predominant cell type in the tumor stroma. Previous studies have shown that the actin-binding protein palladin is highly expressed in the stroma of pancreas tumors, but the interpretation of these results is complicated by the fact that palladin exists as multiple isoforms. In the current study, the expression and localization of palladin isoform 4 was examined in normal specimens and adenocarcinomas of human pancreas, lung, colon, and stomach samples. Immunohistochemistry with isoform-selective antibodies revealed that expression of palladin isoform 4 was higher in adenocarcinomas versus normal tissues, and highest in CAFs. Immunohistochemistry staining revealed that palladin was present in both the cytoplasm and the nucleus of CAFs, and this was confirmed using immunofluorescence staining and subcellular fractionation of a pancreatic CAF cell line. To investigate the functional significance of nuclear palladin, RNA Seq analysis of palladin knockdown CAFs versus control CAFs was performed, and the results showed that palladin regulates the expression of genes involved in the biosynthesis and assembly of collagen, and organization of the extracellular matrix. These results suggested that palladin isoform 4 may play a conserved role in establishing the phenotype of CAFs in multiple tumor types.
Department of Cell Biology and Physiology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Austin R
AR
Cannon
Department of Cell Biology and Physiology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.|Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Meredith K
MK
Owen
Department of Cell Biology and Physiology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.|Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Michael S
MS
Guerrero
Department of Cell Biology and Physiology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.|Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Michael L
ML
Kerber
Department of Biological Sciences, University of Toledo, Toledo, Ohio.
Silvia M
SM
Goicoechea
Department of Cell Biology and Physiology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Kathryn C
KC
Hemstreet
Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Brian
B
Klazynski
Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Johnathan
J
Hollyfield
Department of Cell Biology and Physiology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.|Kidney Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Emily H
EH
Chang
Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas.
Rosa F
RF
Hwang
Department of Cell Biology and Physiology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.|Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Carol A
CA
Otey
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.|Department of Surgery, UNC School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Hong Jin
HJ
Kim
D000230:Adenocarcinoma / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D014407:Tumor Cells, Cultured; D059016:Tumor Microenvironment
D003598:Cytoskeletal Proteins; C412722:PALLD protein, human; D010750:Phosphoproteins; D020033:Protein Isoforms
adenocarcinoma; cancer-associated fibroblast; myofibroblast; pancreas cancer; tumor-associated fibroblast