title: A switch from CD44⁺ cell to EMT cell drives the metastasis of prostate cancer.
abstract: Epithelial-mesenchymal transition (EMT) has been linked to cancer stem-like (CD44+) cell in the prostate cancer (PCa) metastasis. However, the molecular mechanism remains elusive. Here, we found EMT contributed to metastasis in PCa patients failed in androgen deprivation therapy (ADT). Castration TRAMP model also proved PCa treated with ADT promoted EMT with increased CD44+ stem-like cells. Switched CD44+ cell to EMT cell is a key step for luminal PCa cell metastasis. Our results also suggested ADT might go through promoting TGFβ1-CD44 signaling to enhance swift to EMT. Targeting CD44 with salinomycin and siRNA could inhibit cell transition and decrease PCa invasion. Together, cancer stem-like (CD44+) cells could be the initiator cells of EMT modulated by TGFβ1-CD44 signaling. Combined therapy of ADT with anti-CD44 may become a new potential therapeutic approach to battle later stage PCa.
authors.affiliation: Sex Hormone Research Center, Tianjin Institute of Urology, the Second Hospital of Tianjin Medical University, Tianjin, China.
authors.forename: Zhiqun
authors.initials: Z
authors.lastname: Shang
authors.affiliation: Sex Hormone Research Center, Tianjin Institute of Urology, the Second Hospital of Tianjin Medical University, Tianjin, China.
authors.forename: Qiliang
authors.initials: Q
authors.lastname: Cai
authors.affiliation: Sex Hormone Research Center, Tianjin Institute of Urology, the Second Hospital of Tianjin Medical University, Tianjin, China.
authors.forename: Minghao
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Sex Hormone Research Center, Tianjin Institute of Urology, the Second Hospital of Tianjin Medical University, Tianjin, China.
authors.forename: Shimiao
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Sex Hormone Research Center, Tianjin Institute of Urology, the Second Hospital of Tianjin Medical University, Tianjin, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Sex Hormone Research Center, Tianjin Institute of Urology, the Second Hospital of Tianjin Medical University, Tianjin, China.
authors.forename: Libin
authors.initials: L
authors.lastname: Sun
authors.affiliation: Sex Hormone Research Center, Tianjin Institute of Urology, the Second Hospital of Tianjin Medical University, Tianjin, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Jiang
authors.affiliation: Sex Hormone Research Center, Tianjin Institute of Urology, the Second Hospital of Tianjin Medical University, Tianjin, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Tian
authors.affiliation: University of Rochester, Rochester, New York, USA.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Niu
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Life Sciences, Nankai university, Tianjin, China.
authors.forename: Jiatong
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Urology, Changhai Hospital of the Second Military Medical University, Shanghai, China.
authors.forename: Yinghao
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Sex Hormone Research Center, Tianjin Institute of Urology, the Second Hospital of Tianjin Medical University, Tianjin, China.
authors.forename: Yuanjie
authors.initials: Y
authors.lastname: Niu
mesh_terms: D000726:Androgen Antagonists / Q000627:therapeutic use; D000818:Animals; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008954:Models, Biological; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009919:Orchiectomy; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D014746:Vimentin / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000726:Androgen Antagonists; D015820:Cadherins; D018960:Hyaluronan Receptors; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D014746:Vimentin