title: Keratin 17 Is Induced in Oral Cancer and Facilitates Tumor Growth.
abstract: Keratin subtypes are selectively expressed depending on the cell type. They not only provide structural support, but regulate the metabolic processes and signaling pathways that control the growth of the epithelium. KRT17 (keratin 17) is induced in the regenerative epithelium and acts on diverse signaling pathways. Here, we demonstrate that KRT17 is invariably and permanently induced in oral squamous cell carcinoma (OSCC), as revealed by immunohistochemistry and cDNA microarray analysis. Two representative OSCC cell lines; KRT17-weakly expressing Ca9-22 and KRT17-highly expressing HSC3 were used to establish KRT17-overexpressing Ca9-22 and KRT17-knockdown HSC3 cells. Analysis of these cells revealed that KRT17 promoted cell proliferation and migration by stimulating the Akt/mTOR pathway. KRT17 also upregulated the expression of SLC2A1 (solute carrier family 2 member 1/Glut1) and glucose uptake. To further investigate the effect of KRT17 on tumorigenesis, KRT17-knockout HSC3 cells were established and were transplanted to the cephalic skin of nude mice. The tumors that developed from KRT17-knockout HSC3 cells had a lower Ki-67 labeling index and were significantly smaller compared to the controls. These results indicate that KRT17 stimulates the Akt/mTOR pathway and glucose uptake, thereby facilitating tumor growth. We could not confirm the relationship between KRT17 and SFN (stratifin) in the cells examined in this study. However, our study reinforces the concept that the cellular properties of cancer are regulated by a series of molecules similar to those found in wound healing. In OSCC, KRT17 acts as a pathogenic keratin that facilitates tumor growth through the stimulation of multiple signaling pathways, highlighting the importance of KRT17 as a multifunctional promoter of tumorigenesis.
authors: Department of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.|Global Center of Excellence (GCOE) Program, "International Research Center for Molecular Science in Tooth and Bone Disease", Tokyo Medical and Dental University, Tokyo, Japan.
authors: Rumana
authors: R
authors: Khanom
authors: Department of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors: Chi Thi Kim
authors: CT
authors: Nguyen
authors: Department of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors: Kou
authors: K
authors: Kayamori
authors: Department of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors: Xin
authors: X
authors: Zhao
authors: Department of Oral and Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors: Keiichi
authors: K
authors: Morita
authors: Department of Molecular Genetics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.|Global Center of Excellence (GCOE) Program, "International Research Center for Molecular Science in Tooth and Bone Disease", Tokyo Medical and Dental University, Tokyo, Japan.
authors: Yoshio
authors: Y
authors: Miki
authors: Department of Nursing Science, Faculty of Human Care, Tohto College of Health Sciences, Saitama, Japan.
authors: Ken-Ichi
authors: K
authors: Katsube
authors: Department of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.|Oral Health Science Center, Tokyo Dental College, Tokyo, Japan.|Global Center of Excellence (GCOE) Program, "International Research Center for Molecular Science in Tooth and Bone Disease", Tokyo Medical and Dental University, Tokyo, Japan.
authors: Akira
authors: A
authors: Yamaguchi
authors: Department of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
authors: Kei
authors: K
authors: Sakamoto
mesh_terms: D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016022:Case-Control Studies; D002465:Cell Movement; D049109:Cell Proliferation; D005500:Follow-Up Studies; D006801:Humans; D053537:Keratin-17 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; D053537:Keratin-17; D012333:RNA, Messenger