Epithelial cell adhesion molecule (EpCAM) is associated with prostate cancer metastasis and chemo/radioresistance via the PI3K/Akt/mTOR signaling pathway.
Prostate cancer (CaP) is the second leading malignancy in men. The role of epithelial cell adhesion molecule (EpCAM), also known as CD326, in CaP progression and therapeutic resistance is still uncertain. Here, we aimed to investigate the roles of EpCAM in CaP metastasis and chemo/radioresistance. Expression of EpCAM in CaP cell lines and human CaP tissues was assessed using immunofluorescence and immunohistochemistry, respectively. EpCAM was knocked down (KD) in PC-3, DU145 and LNCaP-C4-2B cells using small interfering RNA (siRNA), and KD results were confirmed by confocal microscope, Western blotting and quantitative real time polymerase chain reaction (qRT-PCR). Cell growth was evaluated by proliferation and colony formation assays. The invasive potential was assessed using a matrigel chamber assay. Tumorigenesis potential was measured by a sphere formation assay. Chemo-/radiosensitivity were measured using a colony formation assay. Over-expression of EpCAM was found in primary CaP tissues and lymph node metastases including cancer cells and surrounding stromal cells. KD of EpCAM suppressed CaP proliferation and invasive ability, reduced sphere formation, enhanced chemo-/radiosensitivity, and down-regulated E-cadherin, p-Akt, p-mTOR, p-4EBP1 and p-S6K expression in CaP cells. Our findings suggest that EpCAM plays an important role in CaP proliferation, invasion, metastasis and chemo-/radioresistance associated with the activation of the PI3K/Akt/mTOR signaling pathway and is a novel therapeutic target to sensitize CaP cells to chemo-/radiotherapy.
Cancer Care Centre and Prostate Cancer Institute, St George Hospital, Kogarah, NSW 2217, Australia; St George Clinical School, University of New South Wales (UNSW), Kensington, NSW 2052, Australia.
Jie
J
Ni
Paul
P
Cozzi
Jingli
J
Hao
Julia
J
Beretov
Lei
L
Chang
Wei
W
Duan
Sarah
S
Shigdar
Warick
W
Delprado
Peter
P
Graham
Joseph
J
Bucci
John
J
Kearsley
Yong
Y
Li
D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D000071858:Epithelial Cell Adhesion Molecule; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011836:Radiation Tolerance; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D014162:Transfection
D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C499379:EPCAM protein, human; C546842:MTOR protein, human
3,3′ diaminobenzidine; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; BPH; BSA; CPTC; CRPC; CSC; CTC; CaP; Chemoresistance; DAB; DOX; DTX; ECL; EMT; EpCAM; EpCAM (CD326); FBS; HGPIN; HRP; KD; MAb; MMRD; MTT; Metastasis; PI; PI3K/Akt/mTOR; PSA; PTX; PVDF; Prostate cancer; RP; RT; Radioresistance; SD; TBS; TMA; Tris-buffered saline; benign prostate hyperplasia; bovine serum albumin; cancer stem cell; castration-resistant prostate cancer; circulating prostate tumor cells; circulating tumor cell; docetaxel; doxorubicin; enhanced chemiluminescence; epithelial cell adhesion molecule; epithelial–mesenchymal transition; fetal bovine serum; high-grade prostatic intraepithelial neoplasia; horseradish peroxide; i.c.; intracardiac; knock down; mismatch repair deficient; monoclonal antibody; o/n; overnight; paclitaxel; polyvinylidene difluoride; propidium iodide; prostate cancer; prostate specific antigen; qRT-PCR; quantitative real time polymerase chain reaction; radical prostatectomy; room temperature; s.c.; scr; scrambled; siRNA; small interfering RNA; standard deviation; subcutaneous; tissue microarray