Pseudopod-associated protein KIF20B promotes Gli1-induced epithelial-mesenchymal transition modulated by pseudopodial actin dynamic in human colorectal cancer
Wen-Feng Lin
Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University; Shanghai Institute of Digestive Disease, Shanghai, China
Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang Province, China
Search for more papers by this authorXiao-Lu Lin
Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University; Shanghai Institute of Digestive Disease, Shanghai, China
Department of Digestive Endoscopy, Fujian Provincial Hospital, Provincial Clinic Medical College, Fujian Medical University, Fuzhou, China
Search for more papers by this authorSeng-Wang Fu
Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China
Search for more papers by this authorLi Yang
Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University; Shanghai Institute of Digestive Disease, Shanghai, China
Search for more papers by this authorChao-Tao Tang
Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University; Shanghai Institute of Digestive Disease, Shanghai, China
Search for more papers by this authorYun-Jie Gao
Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University; Shanghai Institute of Digestive Disease, Shanghai, China
Search for more papers by this authorHao-Yan Chen
Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University; Shanghai Institute of Digestive Disease, Shanghai, China
Search for more papers by this authorCorresponding Author
Zhi-Zheng Ge
Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University; Shanghai Institute of Digestive Disease, Shanghai, China
Correspondence
Zhi-zheng Ge, Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University; Shanghai Institute of Digestive Disease, Shanghai, China.
Email: [email protected]
Search for more papers by this authorWen-Feng Lin
Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University; Shanghai Institute of Digestive Disease, Shanghai, China
Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang Province, China
Search for more papers by this authorXiao-Lu Lin
Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University; Shanghai Institute of Digestive Disease, Shanghai, China
Department of Digestive Endoscopy, Fujian Provincial Hospital, Provincial Clinic Medical College, Fujian Medical University, Fuzhou, China
Search for more papers by this authorSeng-Wang Fu
Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China
Search for more papers by this authorLi Yang
Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University; Shanghai Institute of Digestive Disease, Shanghai, China
Search for more papers by this authorChao-Tao Tang
Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University; Shanghai Institute of Digestive Disease, Shanghai, China
Search for more papers by this authorYun-Jie Gao
Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University; Shanghai Institute of Digestive Disease, Shanghai, China
Search for more papers by this authorHao-Yan Chen
Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University; Shanghai Institute of Digestive Disease, Shanghai, China
Search for more papers by this authorCorresponding Author
Zhi-Zheng Ge
Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University; Shanghai Institute of Digestive Disease, Shanghai, China
Correspondence
Zhi-zheng Ge, Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University; Shanghai Institute of Digestive Disease, Shanghai, China.
Email: [email protected]
Search for more papers by this authorAbstract
Kinesin family member 20B (KIF20B) has been reported to have an oncogenic role in bladder and hepatocellular cancer cells, but its role in colorectal cancer (CRC) progression remains unclear. In this study, we assessed the mRNA and protein levels of KIF20B in CRC tissues using qRT-PCR and immunohistochemistry, respectively. KIF20B was overexpressed in CRC tissues and was associated with cancer invasion and metastasis. Mechanistically, KIF20B overexpression promoted the epithelial-mesenchymal transition (EMT) process mediated by glioma-associated oncogene 1 (Gli1) as well as CRC cell migration and invasion. Interestingly, KIF20B was localized in pseudopod protrusions of CRC cells and influenced the formation of cell protrusions, especially the EMT-related invadopodia. Moreover, intracellular actin dynamic participated in the modulation of the Gli1-mediated EMT and EMT-related cell pseudopod protrusion formation induced by KIF20B. We identified a role for KIF20B in CRC progression and revealed a correlation between KIF20B expression in CRC tissues and patient prognosis. The underlying mechanism was associated with the Gli1-mediated EMT and EMT-related cell protrusion formation modulated by intracellular actin dynamic. Thus, KIF20B may be a potential biomarker and promising treatment target for CRC.
Supporting Information
Additional Supporting Information may be found online in the supporting information tab for this article.
| Filename | Description |
|---|---|
| mc22812-sup-0001-SupData-S1.pdf115.7 KB |
Fig. S1. A-B. RT-PCR and Western blotting analyses were used to determine KIF20B expression in CRC cell lines. Table S1. KIF20B expression in colorectal tumor and peritumoral tissues. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
REFERENCES
- 1 Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011; 61: 69–90.
- 2 Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN. Int J Cancer. 2008; 127: 2893–2917.
- 3 Ahn J, Sinha R, Pei Z, et al. Human gut microbiome and risk for colorectal cancer. J Natl Cancer Inst. 2013; 105: 1907–1911.
- 4 Kozovska Z, Gabrisova V, Kucerova L. Colon cancer: cancer stem cells markers, drug resistance and treatment. Biomed Pharmacother. 2014; 68: 911–916.
- 5 Cunningham D, Atkin W, Lenz HJ, et al. Colorectal cancer. Lancet (London, England). 2010; 375: 1030–1047.
- 6 Gallagher DJ, Kemeny N. Metastatic colorectal cancer: from improved survival to potential cure. Oncology. 2010; 78: 237–248.
- 7 Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013; 63: 11–30.
- 8 Nanashima A, Yamaguchi H, Sawai T, et al. Expression of adhesion molecules in hepatic metastases of colorectal carcinoma: relationship to primary tumours and prognosis after hepatic resection. J Gastroenterol Hepatol. 1999; 14: 1004–1009.
- 9 Ohji Y, Yao T, Eguchi T, et al. Evaluation of risk of liver metastasis in colorectal adenocarcinoma based on the combination of risk factors including CD10 expression: multivariate analysis of clinicopathological and immunohistochemical factors. Oncol Rep. 2007; 17: 525–530.
- 10 Tu H, Ahearn TU, Daniel CR, Gonzalez-Feliciano AG, Seabrook ME, Bostick RM. Transforming growth factors and receptor as potential modifiable pre-neoplastic biomarkers of risk for colorectal neoplasms. Mol Carcinog. 2015; 54: 821–830.
- 11 Barozzi C, Ravaioli M, D'Errico A, et al. Relevance of biologic markers in colorectal carcinoma: a comparative study of a broad panel. Cancer. 2002; 94: 647–657.
- 12 Yu Y, Feng YM. The role of kinesin family proteins in tumorigenesis and progression: potential biomarkers and molecular targets for cancer therapy. Cancer. 2010; 116: 5150–5160.
- 13 Goldstein LS, Philp AV. The road less traveled: emerging principles of kinesin motor utilization. Annu Rev Cell Dev Biol. 1999; 15: 141–183.
- 14 Abaza A, Soleilhac JM, Westendorf J, et al. M phase phosphoprotein 1 is a human plus-end-directed kinesin-related protein required for cytokinesis. J Biol Chem. 2003; 278: 27844–27852.
- 15 Kanehira M, Katagiri T, Shimo A, et al. Oncogenic role of MPHOSPH1, a cancer-testis antigen specific to human bladder cancer. Cancer Res. 2007; 67: 3276–3285.
- 16 Liu XR, Cai Y, Cao X, et al. A new oncolytic adenoviral vector carrying dual tumour suppressor genes shows potent anti-tumour effect. J Cell Mol Med. 2012; 16: 1298–1309.
- 17 Liu X, Zhou Y, Liu X, et al. MPHOSPH1: a potential therapeutic target for hepatocellular carcinoma. Cancer Res. 2014; 74: 6623–6634.
- 18 Sapir T, Levy T, Sakakibara A, Rabinkov A, Miyata T, Reiner O. Shootin1 acts in concert with KIF20B to promote polarization of migrating neurons. J Neurosci. 2013; 33: 11932–11948.
- 19 Kalluri R, Weinberg RA. The basics of epithelial-mesenchymal transition. J Clin Invest. 2009; 119: 1420–1428.
- 20 Bates RC, Mercurio AM. The epithelial-mesenchymal transition (EMT) and colorectal cancer progression. Cancer Biol Ther. 2005; 4: 365–370.
- 21 Li L, Li W. Epithelial-mesenchymal transition in human cancer: comprehensive reprogramming of metabolism, epigenetics, and differentiation. Pharmacol Ther. 2015; 150: 33–46.
- 22 Malik G, Knowles LM, Dhir R, et al. Plasma fibronectin promotes lung metastasis by contributions to fibrin clots and tumor cell invasion. Cancer Res. 2010; 70: 4327–4334.
- 23 He M, Subramanian R, Bangs F, et al. The kinesin-4 protein Kif7 regulates mammalian Hedgehog signalling by organizing the cilium tip compartment. Nat Cell Biol. 2014; 16: 663–672.
- 24 Cho A, Ko HW, Eggenschwiler JT. FKBP8 cell-autonomously controls neural tube patterning through a Gli2- and Kif3a-dependent mechanism. Dev Biol. 2008; 321: 27–39.
- 25 Eckert MA, Lwin TM, Chang AT, et al. Twist1-induced invadopodia formation promotes tumor metastasis. Cancer Cell. 2011; 19: 372–386.
- 26 Bowden ET, Onikoyi E, Slack R, et al. Co-localization of cortactin and phosphotyrosine identifies active invadopodia in human breast cancer cells. Exp Cell Res. 2006; 312: 1240–1253.
- 27 Schneider P, Bayo-Fina JM, Singh R, et al. Identification of a novel actin-dependent signal transducing module allows for the targeted degradation of GLI1. Nat Commun. 2015; 6: 8023.
- 28 Kamimoto T, Zama T, Aoki R, Muro Y, Hagiwara M. Identification of a novel kinesin-related protein, KRMP1, as a target for mitotic peptidyl-prolyl isomerase Pin1. J Biol Chem. 2001; 276: 37520–37528.
- 29 Gotschel F, Berg D, Gruber W, et al. Synergism between Hedgehog-GLI and EGFR signaling in Hedgehog-responsive human medulloblastoma cells induces downregulation of canonical Hedgehog-target genes and stabilized expression of GLI1. PLoS ONE. 2013; 8: e65403.
- 30 Atwood SX, Li M, Lee A, Tang JY, Oro AE. GLI activation by atypical protein kinase C iota/lambda regulates the growth of basal cell carcinomas. Nature. 2013; 494: 484–488.
- 31 Inaguma S, Riku M, Hashimoto M, et al. GLI1 interferes with the DNA mismatch repair system in pancreatic cancer through BHLHE41-mediated suppression of MLH1. Cancer Res. 2013; 73: 7313–7323.
- 32 El-Zaatari M, Kao JY, Tessier A, et al. Gli1 deletion prevents Helicobacter-induced gastric metaplasia and expansion of myeloid cell subsets. PLoS ONE. 2013; 8: e58935.
- 33 Varnat F, Siegl-Cachedenier I, Malerba M, Gervaz P. Ruiz i Altaba A. Loss of WNT-TCF addiction and enhancement of HH-GLI1 signalling define the metastatic transition of human colon carcinomas. EMBO Mol Med. 2010; 2: 440–457.
- 34 Zheng X, Vittar NB, Gai X, et al. The transcription factor GLI1 mediates TGFbeta1 driven EMT in hepatocellular carcinoma via a SNAI1-dependent mechanism. PLoS ONE. 2012; 7: e49581.
- 35 Shankar J, Messenberg A, Chan J, Underhill TM, Foster LJ, Nabi IR. Pseudopodial actin dynamic control epithelial-mesenchymal transition in metastatic cancer cells. Cancer Res. 2010; 70: 3780–3790.
- 36 Kim DS, Hubbard SL, Peraud A, Salhia B, Sakai K, Rutka JT. Analysis of mammalian septin expression in human malignant brain tumors. Neoplasia. 2004; 6: 168–178.
- 37 Wang G, Wang X, Wang S, et al. Colorectal cancer progression correlates with upregulation of S100A11 expression in tumor tissues. Int J Colorectal Dis. 2008; 23: 675–682.
- 38 Tian T, Hao J, Xu A, et al. Determination of metastasis-associated proteins in non-small cell lung cancer by comparative proteomic analysis. Cancer Sci. 2007; 98: 1265–1274.
- 39 Li DQ, Wang L, Fei F, et al. Identification of breast cancer metastasis-associated proteins in an isogenic tumor metastasis model using two-dimensional gel electrophoresis and liquid chromatography-ion trap-mass spectrometry. Proteomics. 2006; 6: 3352–3368.
- 40 Chang HJ, Lee MR, Hong SH, et al. Identification of mitochondrial FoF1-ATP synthase involved in liver metastasis of colorectal cancer. Cancer Sci. 2007; 98: 1184–1191.
- 41 Nakatsura T, Senju S, Ito M, Nishimura Y, Itoh K. Cellular and humoral immune responses to a human pancreatic cancer antigen, coactosin-like protein, originally defined by the SEREX method. Eur J Immunol. 2002; 32: 826–836.
- 42 Cimino D, Fuso L, Sfiligoi C, et al. Identification of new genes associated with breast cancer progression by gene expression analysis of predefined sets of neoplastic tissues. Int J Cancer. 2008; 123: 1327–1338.
- 43 Carlson SG, Eng E, Kim EG, Perlman EJ, Copeland TD, Ballermann BJ. Expression of SET, an inhibitor of protein phosphatase 2A, in renal development and Wilms’ tumor. J Am Soc Nephrol. 1998; 9: 1873–1880.
- 44 Tsai YS, Jou YC, Lee GF, et al. Aberrant prothymosin-alpha expression in human bladder cancer. Urology. 2009; 73: 188–192.
- 45 Khoury H, Dankort DL, Sadekova S, Naujokas MA, Muller WJ, Park M. Distinct tyrosine autophosphorylation sites mediate induction of epithelial mesenchymal like transition by an activated ErbB-2/Neu receptor. Oncogene. 2001; 20: 788–799.
- 46 Sun BO, Fang Y, Li Z, Chen Z, Xiang J. Role of cellular cytoskeleton in epithelial-mesenchymal transition process during cancer progression. Biomed Rep. 2015; 3: 603–610.
- 47 Oyanagi J, Ogawa T, Sato H, Higashi S, Miyazaki K. Epithelial-mesenchymal transition stimulates human cancer cells to extend microtubule-based invasive protrusions and suppresses cell growth in collagen gel. PLoS ONE. 2012; 7: e53209.
- 48 Whipple RA, Matrone MA, Cho EH, et al. Epithelial-to-mesenchymal transition promotes tubulin detyrosination and microtentacles that enhance endothelial engagement. Cancer Res. 2010; 70: 8127–8137.
- 49 Provost P, Doucet J, Stock A, Gerisch G, Samuelsson B, Radmark O. Coactosin-like protein, a human F-actin-binding protein: critical role of lysine-75. Biochem J. 2001; 359: 255–263.
- 50 Tak H, Jang E, Kim SB, et al. 14-3-3epsilon inhibits MK5-mediated cell migration by disrupting F-actin polymerization. Cell Signal. 2007; 19: 2379–2387.
- 51 Lin JJ, Eppinga RD, Warren KS, McCrae KR. Human tropomyosin isoforms in the regulation of cytoskeleton functions. Adv Exp Med Biol. 2008; 644: 201–222.
- 52 Chacko AD, Hyland PL, McDade SS, Hamilton PW, Russell SH, Hall PA. SEPT9_v4 expression induces morphological change, increased motility and disturbed polarity. J Pathol. 2005; 206: 458–465.
- 53 Benaud C, Gentil BJ, Assard N, et al. AHNAK interaction with the annexin 2/S100A10 complex regulates cell membrane cytoarchitecture. J Cell Biol. 2004; 164: 133–144.
- 54 Zhao XQ, Naka M, Muneyuki M, Tanaka T. Ca(2+)-dependent inhibition of actin-activated myosin ATPase activity by S100C (S100A11), a novel member of the S100 protein family. Biochem Biophys Res Commun. 2000; 267: 77–79.
- 55 Lindemann S, Tolley ND, Eyre JR, Kraiss LW, Mahoney TM, Weyrich AS. Integrins regulate the intracellular distribution of eukaryotic initiation factor 4E in platelets. A checkpoint for translational control. J Biol Chem. 2001; 276: 33947–33951.
- 56 Schoumacher M, Goldman RD, Louvard D, Vignjevic DM. Actin, microtubules, and vimentin intermediate filaments cooperate for elongation of invadopodia. J Cell Biol. 2010; 189: 541–556.
- 57 Noren NK, Liu BP, Burridge K, Kreft B. P120 catenin regulates the actin cytoskeleton via Rho family GTPases. J Cell Biol. 2000; 150: 567–580.
- 58 Yilmaz M, Christofori G. EMT, the cytoskeleton, and cancer cell invasion. Cancer Metastasis Rev. 2009; 28: 15–33.
