Epithelial cell adhesion molecule (EpCAM) is associated with prostate cancer metastasis and chemo/radioresistance via the PI3K/Akt/mTOR signaling pathway期刊界 All Journals 搜尽天下杂志传播学术成果专业期刊搜索期刊信息化学术搜索

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Epithelial cell adhesion molecule (EpCAM) is associated with prostate cancer metastasis and chemo/radioresistance via the PI3K/Akt/mTOR signaling pathway

Authors:	Jie Ni Paul Cozzi Jingli Hao Julia Beretov Lei Chang Wei Duan Sarah Shigdar Warick Delprado Peter Graham Joseph Bucci John Kearsley Yong Li

Institution:	1. Cancer Care Centre and Prostate Cancer Institute, St George Hospital, Kogarah, NSW 2217, Australia;2. St George Clinical School, University of New South Wales (UNSW), Kensington, NSW 2052, Australia;3. Department of Surgery, St George Hospital, Kogarah, NSW 2217, Australia;4. SEALS, Anatomical Pathology, St George Hospital, Gray St Kogarah, NSW 2217, Australia;5. School of Medicine, Deakin University, Waurn Ponds, VIC 3217, Australia;6. Douglass Hanly Moir Pathology, Macquarie Park, NSW 2113, Australia

Abstract:	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.

Keywords:	EpCAM (CD326) Prostate cancer Metastasis Chemoresistance Radioresistance PI3K/Akt/mTOR BPH"} {"#name":"keyword" "$":{"id":"kw0040"} "$$":[{"#name":"text" "_":"benign prostate hyperplasia BSA"} {"#name":"keyword" "$":{"id":"kw0050"} "$$":[{"#name":"text" "_":"bovine serum albumin CaP"} {"#name":"keyword" "$":{"id":"kw0060"} "$$":[{"#name":"text" "_":"prostate cancer CPTC"} {"#name":"keyword" "$":{"id":"kw0070"} "$$":[{"#name":"text" "_":"circulating prostate tumor cells CRPC"} {"#name":"keyword" "$":{"id":"kw0080"} "$$":[{"#name":"text" "_":"castration-resistant prostate cancer CSC"} {"#name":"keyword" "$":{"id":"kw0090"} "$$":[{"#name":"text" "_":"cancer stem cell CTC"} {"#name":"keyword" "$":{"id":"kw0100"} "$$":[{"#name":"text" "_":"circulating tumor cell DAB"} {"#name":"keyword" "$":{"id":"kw0110"} "$$":[{"#name":"text" "_":"3 3′ diaminobenzidine DOX"} {"#name":"keyword" "$":{"id":"kw0120"} "$$":[{"#name":"text" "_":"doxorubicin DTX"} {"#name":"keyword" "$":{"id":"kw0130"} "$$":[{"#name":"text" "_":"docetaxel ECL"} {"#name":"keyword" "$":{"id":"kw0140"} "$$":[{"#name":"text" "_":"enhanced chemiluminescence EMT"} {"#name":"keyword" "$":{"id":"kw0150"} "$$":[{"#name":"text" "_":"epithelial–mesenchymal transition EpCAM"} {"#name":"keyword" "$":{"id":"kw0160"} "$$":[{"#name":"text" "_":"epithelial cell adhesion molecule FBS"} {"#name":"keyword" "$":{"id":"kw0170"} "$$":[{"#name":"text" "_":"fetal bovine serum HGPIN"} {"#name":"keyword" "$":{"id":"kw0180"} "$$":[{"#name":"text" "_":"high-grade prostatic intraepithelial neoplasia HRP"} {"#name":"keyword" "$":{"id":"kw0190"} "$$":[{"#name":"text" "_":"horseradish peroxide i c "} {"#name":"keyword" "$":{"id":"kw0200"} "$$":[{"#name":"text" "_":"intracardiac KD"} {"#name":"keyword" "$":{"id":"kw0210"} "$$":[{"#name":"text" "_":"knock down MAb"} {"#name":"keyword" "$":{"id":"kw0220"} "$$":[{"#name":"text" "_":"monoclonal antibody MMRD"} {"#name":"keyword" "$":{"id":"kw0230"} "$$":[{"#name":"text" "_":"mismatch repair deficient MTT"} {"#name":"keyword" "$":{"id":"kw0240"} "$$":[{"#name":"text" "_":"3-(4 5-dimethylthiazol-2-yl)-2 5-diphenyltetrazolium bromide o/n"} {"#name":"keyword" "$":{"id":"kw0250"} "$$":[{"#name":"text" "_":"overnight PI"} {"#name":"keyword" "$":{"id":"kw0260"} "$$":[{"#name":"text" "_":"propidium iodide PSA"} {"#name":"keyword" "$":{"id":"kw0270"} "$$":[{"#name":"text" "_":"prostate specific antigen PTX"} {"#name":"keyword" "$":{"id":"kw0280"} "$$":[{"#name":"text" "_":"paclitaxel PVDF"} {"#name":"keyword" "$":{"id":"kw0290"} "$$":[{"#name":"text" "_":"polyvinylidene difluoride qRT-PCR"} {"#name":"keyword" "$":{"id":"kw0300"} "$$":[{"#name":"text" "_":"quantitative real time polymerase chain reaction RP"} {"#name":"keyword" "$":{"id":"kw0310"} "$$":[{"#name":"text" "_":"radical prostatectomy RT"} {"#name":"keyword" "$":{"id":"kw0320"} "$$":[{"#name":"text" "_":"room temperature s c "} {"#name":"keyword" "$":{"id":"kw0330"} "$$":[{"#name":"text" "_":"subcutaneous scr"} {"#name":"keyword" "$":{"id":"kw0340"} "$$":[{"#name":"text" "_":"scrambled SD"} {"#name":"keyword" "$":{"id":"kw0350"} "$$":[{"#name":"text" "_":"standard deviation siRNA"} {"#name":"keyword" "$":{"id":"kw0360"} "$$":[{"#name":"text" "_":"small interfering RNA TBS"} {"#name":"keyword" "$":{"id":"kw0370"} "$$":[{"#name":"text" "_":"Tris-buffered saline TMA"} {"#name":"keyword" "$":{"id":"kw0380"} "$$":[{"#name":"text" "_":"tissue microarray
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