Inhibitor of DNA Binding 1 (Id1) Mediates Stemness of Colorectal Cancer Cells Through the Id1-c-Myc-PLAC8 Axis Via the Wnt/β-catenin and Shh Signaling Pathways

Overview

Journal Cancer Manag Res

Publisher Dove Medical Press

Specialty Oncology

Date 2019 Aug 24

PMID 31440083

Citations 20

Authors

Yanxia Sun

Xiaolan Lai

Yue Yu

Jieyu Li

Lei Cao

Wansong Lin

Chuanzhong Huang

Jinrong Liao

Wei Chen

Chao Li

Chunkang Yang

Mingang Ying

Qiang Chen

Yunbin Ye

Affiliations

Soon will be listed here.

Abstract

Background: Inhibitor of DNA binding 1 (Id1) is upregulated in multiple cancers, and Id1overexpression correlates with cancer aggressiveness and poor clinical outcomes in cancer patients. However, its roles in cancer stem-like cells (CSCs) and epithelial-mesenchymal transition (EMT) are still elusive.

Purpose: This study aimed to examine the role of on the mediation of CRC stemness and explore the underlying mechanisms.

Methods: Id1 and CD133 expression was detected by qPCR assay and immunohistochemistry (IHC) in normal mucosal and primary colorectal cancer (CRC) specimens. was stably knocked down (KD) in human CRC cell lines. Spheres forming assay and tumorigenic assay were performed to evaluate self-renewal capacity and tumor initiation. Expression of CSC- and EMT-related markers and TCF/LEF activity were assessed in HCT116 cells after KD.

Results: qPCR assay showed higher and expression in CRC specimens than in normal mucosal specimens (<0.05). IHC detected high cytoplasmic Id1 expression in 35 CRC specimens (46.7%), and high CD133 expression in 22 CRC specimens (29.3%) and negative expression in 18 normal mucosal specimens. High Id1 expression positively correlated with poor differentiation (=0.034), and CD133 expression correlated with T category in CRC patients (=0.002). Spearman correlation analysis revealed a positive correlation between Id1 and CD133 expression in CRC patients (<0.05). KD resulted in suppression of proliferation, cell-colony formation, self-renewal capability and CSC-like features in HCT116 cells, and impaired the tumor-initiating capability in CRC cells. In addition, Id1 maintained the stemness of CRC cells via the Id1-c-Myc-PLAC8 axis through activating the Wnt/β-catenin and Shh signaling pathways.

Conclusions: Id1 expression significantly correlates with CD133 expression in CRC patients, and KD impairs CSC-like capacity and reverses EMT traits, partially via the Wnt/β-catenin signaling. Id1 may be a promising therapeutic target against colon CSCs.

Citing Articles

BRAF mutations and the association of V600E with CD133 and CDX2 expression in a Pakistani colorectal carcinoma cohort.

Hassan S, Mirza T, Khatoon A, Bukhari U, Shaikh F, Karim A BMC Cancer. 2024; 24(1):1162.

PMID: 39300378 PMC: 11411998. DOI: 10.1186/s12885-024-12925-z.

Autophagy-mediated ID1 turnover dictates chemo-resistant fate in ovarian cancer stem cells.

Phadte P, Bishnu A, Dey P, M M, Mehrotra M, Singh P J Exp Clin Cancer Res. 2024; 43(1):222.

PMID: 39123206 PMC: 11316295. DOI: 10.1186/s13046-024-03147-z.

Detailed survey of an intestinal epithelium model by single-cell transcriptomics.

Ran R, Briones J, Jena S, Anderson N, Olson M, Green L iScience. 2024; 27(4):109383.

PMID: 38523788 PMC: 10959667. DOI: 10.1016/j.isci.2024.109383.

Orai3 Calcium Channel Contributes to Oral/Oropharyngeal Cancer Stemness through the Elevation of ID1 Expression.

Nguyen A, Sung Y, Lee S, Martin C, Srikanth S, Chen W Cells. 2023; 12(18).

PMID: 37759448 PMC: 10527097. DOI: 10.3390/cells12182225.

Transcription factor 3 promotes migration and invasion potential and maintains cancer stemness by activating ID1 expression in esophageal squamous cell carcinoma.

Li Z, Sun M, Fang K, Zhao Z, Leng Z, Zhang Z Cancer Biol Ther. 2023; 24(1):2246206.

PMID: 37607071 PMC: 10443991. DOI: 10.1080/15384047.2023.2246206.

References

Lasorella A, Uo T, Iavarone A . Id proteins at the cross-road of development and cancer. Oncogene. 2002; 20(58):8326-33. DOI: 10.1038/sj.onc.1205093. View

Schoppmann S, Schindl M, Bayer G, Aumayr K, Dienes J, Horvat R . Overexpression of Id-1 is associated with poor clinical outcome in node negative breast cancer. Int J Cancer. 2003; 104(6):677-82. DOI: 10.1002/ijc.11009. View

Zhang X, Ling M, Wang X, Wong Y . Inactivation of Id-1 in prostate cancer cells: A potential therapeutic target in inducing chemosensitization to taxol through activation of JNK pathway. Int J Cancer. 2005; 118(8):2072-81. DOI: 10.1002/ijc.21592. View

Takayama T, Miyanishi K, Hayashi T, Sato Y, Niitsu Y . Colorectal cancer: genetics of development and metastasis. J Gastroenterol. 2006; 41(3):185-92. DOI: 10.1007/s00535-006-1801-6. View

In Yook J, Li X, Ota I, Hu C, Kim H, Kim N . A Wnt-Axin2-GSK3beta cascade regulates Snail1 activity in breast cancer cells. Nat Cell Biol. 2006; 8(12):1398-406. DOI: 10.1038/ncb1508. View

Ricci-Vitiani L, Lombardi D, Pilozzi E, Biffoni M, Todaro M, Peschle C . Identification and expansion of human colon-cancer-initiating cells. Nature. 2006; 445(7123):111-5. DOI: 10.1038/nature05384. View

OBrien C, Pollett A, Gallinger S, Dick J . A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature. 2006; 445(7123):106-10. DOI: 10.1038/nature05372. View

Ling M, Wang X, Zhang X, Wong Y . The multiple roles of Id-1 in cancer progression. Differentiation. 2006; 74(9-10):481-7. DOI: 10.1111/j.1432-0436.2006.00083.x. View

Katoh Y, Katoh M . Comparative genomics on PROM1 gene encoding stem cell marker CD133. Int J Mol Med. 2007; 19(6):967-70. View

10.

Spillane J, Henderson M . Cancer stem cells: a review. ANZ J Surg. 2007; 77(6):464-8. DOI: 10.1111/j.1445-2197.2007.04096.x. View

11.

Forootan S, Wong Y, Dodson A, Wang X, Lin K, Smith P . Increased Id-1 expression is significantly associated with poor survival of patients with prostate cancer. Hum Pathol. 2007; 38(9):1321-9. DOI: 10.1016/j.humpath.2007.02.011. View

12.

Asirvatham A, Carey J, Chaudhary J . ID1-, ID2-, and ID3-regulated gene expression in E2A positive or negative prostate cancer cells. Prostate. 2007; 67(13):1411-20. DOI: 10.1002/pros.20633. View

13.

Zhao Z, Zhang Z, Zhang H, Jiang L, Wang M, Sun X . Overexpression of Id-1 protein is a marker in colorectal cancer progression. Oncol Rep. 2008; 19(2):419-24. View

14.

Gil J, Stembalska A, Pesz K, Sasiadek M . Cancer stem cells: the theory and perspectives in cancer therapy. J Appl Genet. 2008; 49(2):193-9. DOI: 10.1007/BF03195612. View

15.

Lee J, Kang M, Jang S, Qian T, Kim H, Kim C . Id-1 activates Akt-mediated Wnt signaling and p27(Kip1) phosphorylation through PTEN inhibition. Oncogene. 2008; 28(6):824-31. DOI: 10.1038/onc.2008.451. View

16.

Zhu L, Gibson P, Currle D, Tong Y, Richardson R, Bayazitov I . Prominin 1 marks intestinal stem cells that are susceptible to neoplastic transformation. Nature. 2008; 457(7229):603-7. PMC: 2633030. DOI: 10.1038/nature07589. View

17.

Yamashita T, Ji J, Budhu A, Forgues M, Yang W, Wang H . EpCAM-positive hepatocellular carcinoma cells are tumor-initiating cells with stem/progenitor cell features. Gastroenterology. 2009; 136(3):1012-24. PMC: 2828822. DOI: 10.1053/j.gastro.2008.12.004. View

18.

Debeb B, Xu W, Woodward W . Radiation resistance of breast cancer stem cells: understanding the clinical framework. J Mammary Gland Biol Neoplasia. 2009; 14(1):11-7. DOI: 10.1007/s10911-009-9114-z. View

19.

Hu H, Han H, Wang Y, Zhang X, Chua C, Wong Y . The role of Id-1 in chemosensitivity and epirubicin-induced apoptosis in bladder cancer cells. Oncol Rep. 2009; 21(4):1053-9. DOI: 10.3892/or_00000323. View

20.

MacDonald B, Tamai K, He X . Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell. 2009; 17(1):9-26. PMC: 2861485. DOI: 10.1016/j.devcel.2009.06.016. View