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中华细胞与干细胞杂志(电子版) ›› 2017, Vol. 07 ›› Issue (02) : 112 -116. doi: 10.3877/cma.j.issn.2095-1221.2017.02.009

所属专题: 文献

综述

上皮干细胞参与肿瘤恶变的机制
张诗惠1, 胡琼2, 谢富安3, 洪笑迁2, 刘宽灿4,()   
  1. 1. 410083 长沙,中南大学本科生院
    2. 350025 福州,厦门大学附属东方医院检验科
    3. 350025 福州总医院全军临床检验医学研究所
    4. 350025 福州,厦门大学附属东方医院检验科;350025 福州总医院全军临床检验医学研究所
  • 收稿日期:2016-10-31 出版日期:2017-04-01
  • 通信作者: 刘宽灿
  • 基金资助:
    国家自然科学基金(81302068); 国家863青年科学家专题(2014AA020541); 福建省国际合作重点项目(2017I0014)

Involvement of epithelial stem cells in malignant transformation and mechanisms

Shihui Zhang1, Qiong Hu2, Fuan Xie3, Xiaoqian Hong2, Kuancan Liu4,()   

  1. 1. Undergraduate School, Zhongnan University, Changsha 410012, China
    2. Department of Laboratory Medicine, Dongfang Hospital, Xiamen University, Fuzhou 350025, China
    3. Institute for Laboratory Medicine, Fuzhou General Hospital, Fuzhou 350025, China
    4. Department of Laboratory Medicine, Dongfang Hospital, Xiamen University, Fuzhou 350025, China; Institute for Laboratory Medicine, Fuzhou General Hospital, Fuzhou 350025, China
  • Received:2016-10-31 Published:2017-04-01
  • Corresponding author: Kuancan Liu
  • About author:
    Corresponding author: Liu Kuancan, Email:
引用本文:

张诗惠, 胡琼, 谢富安, 洪笑迁, 刘宽灿. 上皮干细胞参与肿瘤恶变的机制[J]. 中华细胞与干细胞杂志(电子版), 2017, 07(02): 112-116.

Shihui Zhang, Qiong Hu, Fuan Xie, Xiaoqian Hong, Kuancan Liu. Involvement of epithelial stem cells in malignant transformation and mechanisms[J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2017, 07(02): 112-116.

上皮干细胞是一类具有自我更新能力和多向分化潜能的细胞,在维持上皮稳定中起到关键作用。随着研究不断深入,发现上皮干细胞可作为上皮肿瘤发生的起始细胞,上皮干细胞恶变不仅受干细胞微环境影响,它还与多条信号通路失调及基因突变相关。但上皮干细胞如何恶变为肿瘤的具体机制依旧不清楚。本文就上皮干细胞和肿瘤干细胞两者的联系以及上皮干细胞恶变为肿瘤的作用机制进行阐述。

Epithelial stem cells, which have the ability of self-renewal and multiple differentiation, play a crucial role in maintaining epithelial tissue homeostasis. Recently, many studies have showed that epithelial stem cells may be the tumour-initiating cells. The transformation of epithelial stem cell is not only affected by the microenvironment, but also promoted by dysregulation of signal pathways and gene mutations. However, the mechanism how epithelial stem cells transform and become tumor cells remains unclear. Here we review the relationships between epithelial stem cells and cancer stem cells and the mechanism of transformation of epithelial stem cells.

表1 上皮组织器官中上皮干细胞和肿瘤干细胞标志物
图1 上皮干细胞与肿瘤发生
图2 参与上皮干细胞增殖的主要信号通路
1
Barker N. Adult intestinal stem cells: critical drivers of epithelial homeostasis and regeneration[J]. Nat Rev Mol Cell Biol, 2014, 15(1):19-33.
2
Shackleton M, Vaillant F, Simpson KJ, et al. Generation of a functional mammary gland from a single stem cell[J]. Nature, 2006, 439(772):84-88.
3
Lawson DA, Xin L, Lukacs RU, et al. Isolation and functional characterization of murine prostate stem cells[J]. Proc Natl Acad Sci U S A, 2007, 104(1):181-186.
4
Deward AD, Cramer J, Lagasse E. Cellular heterogeneity in the mouse esophagus implicates the presence of a nonquiescent epithelial stem cell population[J]. Cell Rep, 2014, 9(2):701-711.
5
Phesse TJ, Clarke AR. Normal stem cells in cancer prone epithelial tissues[J]. Br J Cancer, 2009, 100(2):221-227.
6
Ng A, Barker N. Ovary and fimbrial stem cells: biology, niche and cancer origins[J]. Nat Rev Mol Cell Biol, 2015, 16(10):625-638.
7
Kessler M, Hoffmann K, Brinkmann V, et al. The notch and Wnt pathways regulate stemness and differentiation in human fallopian tube organoids[J]. Nat Commun, 2015, 6:8989-8999.
8
Smalley M, Ashworth A. Stem cells and breast cancer: A field in Transit[J]. Nat Rev Cancer, 2003, 3(11):832-844.
9
Walter D, Lier A, Geiselhart A, et al. Exit from dormancy provokes DNA-damage-induced attrition in haematopoietic stem cells[J]. Nature, 2015, 520(7548):549-552.
10
李红,臧隽章,冯振卿,等. 肿瘤细胞与骨髓源性细胞融合对肿瘤转移的影响及机制[J]. 医学研究生学报, 29(6):658-662.
11
Malanchi I, Peinado H, Kassen D, et al. Cutaneous cancer stem cell maintenance is dependent on beta-catenin signalling[J]. Nature, 2008, 452(7187):U12-650.
12
Jardé T, Kass L, Staples M, et al. ERBB3 Positively Correlates with Intestinal Stem Cell Markers but Marks a Distinct Non Proliferative CellPopulation in Colorectal Cancer[J]. PLoS One, 2015, 10(9):e0138336-e0138351.
13
Swindall AF, Londoño-Joshi AI, Schultz MJ, et al. ST6Gal-I protein expression is upregulated in human epithelial tumors and correlates with stem cell markers in normal tissues and colon cancer cell lines[J]. Cancer Res, 2013, 73(7):2368-2378.
14
Chekhun SV, Zadvorny TV, Tymovska YO, et al. CD44+/CD24-markers of cancer stem cells in patients with breast cancer of different molecular subtypes[J]. Exp Oncol, 2015, 37(1):58-63.
15
Mansour SF, Atwa MM. Clinicopathological significance of CD133 and ALDH1 cancer stem cell marker expression in invasive ductal breast carcinoma[J]. Asian Pac J Cancer Prev, 2015, 16(17):7491-7496.
16
Heerma van Voss MR, van der Groep P, Bart J, et al. Expression of the stem cell marker ALDH1 in the normal breast of BRCA1 mutation carriers[J]. Breast Cancer Res Treat, 2010, 123(2):611-612.
17
Guinot A, Oeztuerk-Winder F, Ventura JJ. miR-17-92/p38 alpha dysregulation enhances Wnt signaling and selects Lgr6(+) cancer stem-like cells during lung adenocarcinoma progression[J]. Cancer Res, 2016, 76(13):4012-4022.
18
Kobayashi I, Takahashi F, Nurwidya F, et al. Oct4 plays a crucial role in the maintenance of gefitinib-resistant lung cancer stem cells[J]. Biochem Biophys Res Commun, 2016, 473(1):125-132.
19
Li T, Su Y, Mei Y, et al. ALDH1A1 is a marker for malignant prostate stem cells and predictor of prostate cancer patients' outcome[J]. Lab Invest, 2010, 90(2):234-244.
20
Collins AT, Berry PA, Hyde C, et al. Prospective identification of tumorigenic prostate cancer stem cells[J]. Cancer Res, 2005, 65(23):10946-10951.
21
Hayakawa Y, Ariyama H, Stancikova J, et al. Mist1 expressing gastric stem cells maintain the normal and neoplastic gastric epithelium and are supported by a perivascular stem cell niche[J]. Cancer Cell, 2015, 28(6):800-814.
22
Li XB, Yang G, Zhu L, et al. Gastric Lgr5(+) stem cells are the cellular origin of invasive intestinal-type gastric cancer in mice[J]. Cell Res, 2016, 26(7):838-849.
23
Zhang XW, Hua RX, Wang XF, et al. Identification of stem-like cells and clinical significance of candidate stem cell markers in gastric cancer[J]. Oncotarget, 2016, 7(9):9815-9831.
24
Zhao XZ, Wang F, Hou MX. Expression of stem cell markers nanog and PSCA in gastric cancer and its significance[J]. Oncol Lett, 2016, 11(1, A):442-448.
25
Snippert HJ, Haegebarth A, Kasper M, et al. Lgr6 marks stem cells in the hair follicle that generate all cell lineages of the skin[J]. Science, 2010, 327(5971):1385-1389.
26
Brownell I, Guevara E, Bai CB, et al. Nerve-Derived sonic hedgehog defines a niche for hair follicle stem cells capable of becoming epidermal stem cells[J]. Cell Stem Cell, 2011, 8(5):552-565.
27
Liu S, Gong Z, Chen M, et al. Lgr5-positive cells are cancer stem cells in skin squamous cell carcinoma[J]. Tumour Biol, 2014, 35(11):11605-11612.
28
Sabet MN, Rakhshan A, Erfani E, et al. Co-Expression of putative cancer stem cell markers, CD133 and nestin, in skin tumors[J]. Asian Pac J Cancer Prev, 2014, 15(19):8161-8169.
29
Von Rahden BH, Kircher S, Lazariotou M, et al. LgR5 expression and cancer stem cell hypothesis:Clue to define the true origin of esophageal adenocarcinomas with and without Barrett's esophagus[J]. J Exp Clin Cancer Res, 2011, 30:23-33.
30
Tomizawa Y, Wu TT, Wang KK. Epithelial mesenchymal transition and cancer stem cells in esophageal adenocarcinoma originating from Barrett's esophagus[J]. Oncol Lett, 2012, 3(5):1059-1063.
31
Florian MC, Geiger H. Concise review: polarity in stem cells, disease, and aging[J]. Stem Cells, 2010, 28(9):1623-1629.
32
Martin-Belmonte F, Perez-Moreno M. Epithelial cell polarity, stem cells and cancer[J]. Nat Rev Cancer, 2012, 12(1):23-38.
33
Knoblich JA. Asymmetric cell division: recent developments and their implications for tumour biology[J]. Nat Rev Mol Cell Biol, 2010, 11(12):849-860.
34
Cicalese A, Bonizzi G, Pasi CE, et al. The tumor suppressor p53 regulates polarity of Self-Renewing divisions in mammary stem cells[J]. Cell, 2009, 138(6):1083-1095.
35
Sato T, Van Es JH, Snippert HJ, et al. Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts[J]. Nature, 2011, 469(7330):415-418.
36
Goodell MA, Nguyen H, Shroyer N. Somatic stem cell heterogeneity: diversity in the blood, skin and intestinal stem cell compartments[J]. Nat Rev Mol Cell Biol, 2015, 16(5):299-309.
37
Yilmaz ÖH, Katajisto P, Lamming DW, et al. mTORC1 in the paneth cell niche couples intestinal stem-cell function to calorie intake[J]. Nature, 2012, 486(744):490-495.
38
Beyaz S, Mana MD, Roper J, et al. High-fat diet enhances stemness and tumorigenicity of intestinal progenitors[J]. Nature, 2016, 531(7592):53-58.
39
Liu KC, Jiang M, Lu Y, et al. Sox2 cooperates with Inflammation-Mediated Stat3 activation in the malignant transformation of foregut basal progenitor cells[J]. Cell Stem Cell, 2013, 12(3):304-315.
40
Arwert EN, Hoste E, Watt FM. Epithelial stem cells, wound healing and cancer[J]. Nat Rev Cancer, 2012, 12(3):170-180.
41
Ayyaz A, Jasper H. Intestinal inflammation and stem cell homeostasis in aging Drosophila melanogaster[J]. Front Cell Infect Microbiol, 2013, 3:98-105.
42
Waldner MJ, Foersch S, Neurath MF. Interleukin-6-A key regulator of colorectal cancer development[J]. Int J Biol Sci, 2012, 8(9):1248-1253.
43
Grachtchouk M, Rong M, Yu S, et al. Basal cell carcinomas in mice overexpressing Gli2 in skin[J]. Nat Genet, 2000, 24(3):216-217.
44
Youssef KK, Van Keymeulen A, Lapouge G, et al. Identification of the cell lineage at the origin of basal cell carcinoma[J]. Nat Cell Biol, 2010, 12(3):299-U111.
45
Wong SY, Reiter JF. Wounding mobilizes hair follicle stem cells to form tumors[J]. Proc Natl Acad Sci U S A, 2011, 108(10):4093-4098.
46
Cordero JB, Stefanatos RK, Scopelliti A, et al. Inducible progenitor-derived Wingless regulates adult midgut regeneration in Drosophila[J]. EMBO J, 2012, 31(19):3901-3917.
47
Thenappan A, Li Y, Shetty K, et al. New therapeutics targeting colon cancer stem cells[J]. Curr Colorectal Cancer Rep, 2009, 5(4):209-220.
48
Barker N, Ridgway RA, Van Es JH, et al. Crypt stem cells as the cells-of-origin of intestinal cancer[J]. Nature, 2009, 457(7229):608-U119.
49
Van Der Heijden M, Zimberlin CD, Nicholson AM, et al. Bcl-2 is a critical mediator of intestinal transformation[J]. Nat Commun, 2016, 7:10916-10926.
50
Scheel C, Eaton EN, Li SH, et al. Paracrine and autocrine signals induce and maintain mesenchymal and stem cell states in the breast[J]. Cell, 2011, 145(6):926-940.
51
Zhang D, Park D, Zhong Y, et al. Stem cell and neurogenic gene-expression profiles Link prostate basal cells to aggressive prostate cancer[J]. Nat Commun, 2016,7:10798-10812.
52
Chang CJ, Chao CH, Xia WY, et al. p53 regulates epithelial-mesenchymal transition and stem cell properties through modulating miRNAs[J]. Nat Cell Biol, 2011, 13(3):317-U296.
53
Decastro AJ, Dunphy KA, Hutchinson J, et al. MiR203 mediates subversion of stem cell properties during mammary epithelial differentiation via repression of DeltaNP63alpha and promotes mesenchymal-to-epithelial transition[J]. Cell Death Dis, 2013,4:e514-e523.
54
刁竞芳,莫嘉强,赵祥, 等. miR-30a-5p对人肝癌干细胞增殖和凋亡的影响[J]. 中华细胞与干细胞杂志(电子版), 2016, 6(1):31-35.
55
刁竞芳,莫嘉强,赵祥, 等. miR-30a-5p对CD133+ Huh7人肝癌干细胞侵袭和迁移能力的影响[J]. 中华细胞与干细胞杂志(电子版), 2016, 6(3):167-173.
56
Visvader JE, Lindeman GJ. Cancer stem cells in solid tumours: accumulating evidence and unresolved questions[J]. Nat Rev Cancer, 2008, 8(10):755-768.
57
Strauss R, Sova P, Liu Y, et al. Epithelial phenotype confers resistance of ovarian cancer cells to oncolytic adenoviruses[J]. Cancer Res, 2009, 69(12):5115-5125.
58
Marhaba R, Klingbeil P, Nuebel T, et al. CD44 and EpCAM: Cancer-Initiating cell markers[J]. Curr Mol Med, 2008, 8(8):784-804.
59
Yin G, Alvero AB, Craveiro V, et al. Constitutive proteasomal degradation of TWIST-1 in epithelial-ovarian cancer stem cells impacts differentiation and metastatic potential[J]. Oncogene, 2013, 32(1):39-49.
60
Grun D, Adhikary G, Eckert RL. VEGF-A acts via neuropilin-1 to enhance epidermal cancer stem cell survival and formation of aggressive and highly vascularized tumors[J]. Oncogene, 2016, 35(33):4379-4387.
61
彭穗,王晶,彭振维, 等. 携带缺氧诱导因子-1α-siRNA的叶酸靶向化的磁性纳米复合物抑制肝癌干细胞增殖的实验研究[J]. 中华细胞与干细胞杂志(电子版), 2016, 6(1):42-46.
62
Oskarsson T, Essers MA, Dubois N, et al. Skin epidermis lacking the c-Myc gene is resistant to Ras-driven tumorigenesis but can reacquire sensitivity upon additional loss of the p21Cip1 gene[J]. Genes Dev, 2006, 20(15):2024-2029.
63
Muncan V, Sansom OJ, Tertoolen L, et al. Rapid loss of intestinal crypts upon conditional deletion of the Wnt/Tcf-4 target gene c-Myc[J]. Mol Cell Biol, 2006, 26(22):8418-8426.
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