IL-13/IL-13RA2 signaling promotes colorectal cancer stem cell tumorigenesis by inducing ubiquitinated degradation of p53

Baoyu He; Jing Liang; Qianqian Qin; Yuqin Zhang; Shuo Shi; Jinghe Cao; Zhixin Zhang; Qingli Bie; Rou Zhao; Li Wei; Baogui Zhang; Bin Zhang

doi:10.1016/j.gendis.2023.01.027

您当前的位置：

首页 >

文章列表页 >

IL-13/IL-13RA2 signaling promotes colorectal cancer stem cell tumorigenesis by inducing ubiquitinated degradation of p53

Full-length article | 更新时间：2024-02-04

- IL-13/IL-13RA2 signaling promotes colorectal cancer stem cell tumorigenesis by inducing ubiquitinated degradation of p53
- Genes & Diseases Vol. 1, Issue 1, Pages: 495-508(2024)
- 作者机构：
  
  1. Department of Laboratory Medicine, Affiliated Hospital of Jining Medical University, Jining Medical University,Shandong,Jining,China,272000
  2. Postdoctoral Mobile Station of Shandong University of Traditional Chinese Medicine,Shandong,Jinan,China,250355
  3. Department of Reproductive Medicine, Affiliated Hospital of Jining Medical University, Jining Medical University,Shandong,Jining,China,272000
  4. Department of Gastrointestinal Surgery, Affiliated Hospital of Jining Medical University, Jining Medical University,Shandong,Jining,China,272000
  5. Institute of Forensic Medicine and Laboratory Medicine, Jining Medical University,Shandong,Jining,China,272067
- 作者简介：
- 基金信息：
- DOI：10.1016/j.gendis.2023.01.027
  CLC：
- Published：2024，
  
  Published Online：1 January 2024，
扫描看全文
Baoyu He, Jing Liang, Qianqian Qin, et al. IL-13/IL-13RA2 signaling promotes colorectal cancer stem cell tumorigenesis by inducing ubiquitinated degradation of p53. [J]. Genes & Diseases 1(1):495-508(2024)
DOI：

Baoyu He, Jing Liang, Qianqian Qin, et al. IL-13/IL-13RA2 signaling promotes colorectal cancer stem cell tumorigenesis by inducing ubiquitinated degradation of p53. [J]. Genes & Diseases 1(1):495-508(2024) DOI： 10.1016/j.gendis.2023.01.027.

摘要

Abstract

Cancer stem cells (CSCs) are considered tumor-initiating cells and the main drivers of disease progression. Targeting these rare cancer cells

however

remains challenging with respect to therapeutic benefit. Here

we report the up-regulation of IL-13RA2 expression in colorectal cancer (CRC) tissues and spheroid cells. The expression of IL-13RA2 was positively correlated with canonical stemness markers in CRC. We further demonstrated that the level of IL-13 was up-regulated in the serum of CRC patients. Biologically

recombinant IL-13 (rIL-13) stimulation promoted the sphere formation

proliferation

and migration of CRC cells

in vitro

and enhanced tumorigenesis

in vivo

. This phenotype could be reversed by knocking down IL-13RA2. Mechanistically

IL-13 activated autophagy by inducing LC3I/LC3II transformation in CRC-CSCs

which was crucial for the biological functions of IL-13. We further demonstrated that IL-13RA2 acted as a modular link of the E3 ligase UBE3C and the substrate p53 protein

enhancing the interaction of UBE3C and p53

thereby inducing the K48-linked ubiquitination of p53. In conclusion

the IL-13/IL-13RA2 signaling cascade promotes CRC-CSC self-renewal and tumorigenesis by inducing p53 ubiquitination

adding an important layer to the connection between IL-13 and p53

which can be translated into novel targeted therapies.

关键词

Keywords

AutophagyColorectal cancer stem cellsIL-13/IL-13RA2 signalingp53Ubiquitinated degradation

references

1 Y. Wang, X. He, H. Nie, et al.Application of artificial intelligence to the diagnosis and therapy of colorectal cancer Am J Cancer Res, 10 (11) (2020), pp. 3575-3598

2 C. Ou, Z. Sun, X. He, et al.Targeting YAP1/LINC00152/FSCN1 signaling axis prevents the progression of colorectal cancer Adv Sci, 7 (3) (2019), Article 1901380

3 B. He, W. Chao, Z. Huang, et al.Hsa_circ_001659 serves as a novel diagnostic and prognostic biomarker for colorectal cancer Biochem Biophys Res Commun, 551 (2021), pp. 100-106

4 E. Vlashi, F. PajonkCancer stem cells, cancer cell plasticity and radiation therapy Semin Cancer Biol, 31 (2015), pp. 28-35

5 M.F. ClarkeClinical and therapeutic implications of cancer stem cells N Engl J Med, 380 (23) (2019), pp. 2237-2245

6 Y. Han, D. Wang, L. Peng, et al.Single-cell sequencing: a promising approach for uncovering the mechanisms of tumor metastasis J Hematol Oncol, 15 (2022), p. 59

7 E. Abad, D. Graifer, A. LyakhovichDNA damage response and resistance of cancer stem cells Cancer Lett, 474 (2020), pp. 106-117

8 X. Li, X. Li, B. Zhang, et al.The role of cancer stem cell-derived exosomes in cancer progression Stem Cell Int, 2022 (2022), Article 9133658

9 T. Dalessandri, G. Crawford, M. Hayes, et al.IL-13 from intraepithelial lymphocytes regulates tissue homeostasis and protects against carcinogenesis in the skin Nat Commun, 7 (2016), Article 12080

10 P. Zhu, X. Zhu, J. Wu, et al.IL-13 secreted by ILC2s promotes the self-renewal of intestinal stem cells through circular RNA circPan3 Nat Immunol, 20 (2) (2019), pp. 183-194

11 Y. Liu, C. Meyer, A. Müller, et al.IL-13 induces connective tissue growth factor in rat hepatic stellate cells via TGF-β-independent Smad signaling J Immunol, 187 (5) (2011), pp. 2814-2823

12 S. Fichtner-Feigl, W. Strober, K. Kawakami, et al.IL-13 signaling through the IL-13alpha2 receptor is involved in induction of TGF-beta 1 production and fibrosis Nat Med, 12 (1) (2006), pp. 99-106

13 M.A. Hallett, K.T. Venmar, B. FingletonCytokine stimulation of epithelial cancer cells: the similar and divergent functions of IL-4 and IL-13 Cancer Res, 72 (24) (2012), pp. 6338-6343

14 B. He, H. Pan, F. Zheng, et al.Long noncoding RNA LINC00930 promotes PFKFB3-mediated tumor glycolysis and cell proliferation in nasopharyngeal carcinoma J Exp Clin Cancer Res, 41 (2022), p. 77

15 B. He, W. Li, Y. Wu, et al.Epstein-Barr virus-encoded miR-BART6-3p inhibits cancer cell metastasis and invasion by targeting long non-coding RNA LOC553103 Cell Death Dis, 7 (9) (2016), Article e2353

16 Y. Hao, B. He, L. Wu, et al.Nuclear translocation of p85β promotes tumorigenesis of PIK3CA helical domain mutant cancer Nat Commun, 13 (2022), p. 1974

17 B. Beck, C. BlanpainUnravelling cancer stem cell potential Nat Rev Cancer, 13 (10) (2013), pp. 727-738

18 V. Plaks, N. Kong, Z. WerbThe cancer stem cell niche: how essential is the niche in regulating stemness of tumor cells? Cell Stem Cell, 16 (3) (2015), pp. 225-238

19 S. Dawood, L. Austin, M. CristofanilliCancer stem cells: implications for cancer therapy Oncology, 28 (12) (2014), pp. 1101-1107 1110

20 K. Eun, S.W. Ham, H. KimCancer stem cell heterogeneity: origin and new perspectives on CSC targeting BMB Rep, 50 (3) (2017), pp. 117-125

21 Z. Liao, H. Nie, Y. Wang, et al.The emerging landscape of long non-coding RNAs in colorectal cancer metastasis Front Oncol, 11 (2021), Article 641343

22 L. Peng, D. Wang, Y. Han, et al.Emerging role of cancer-associated fibroblasts-derived exosomes in tumorigenesis Front Immunol, 12 (2021), Article 795372

23 W.H. MatsuiCancer stem cell signaling pathways Medicine, 95 (1 Suppl 1) (2016), pp. S8-S19

24 P. Mannon, W. ReinischInterleukin 13 and its role in gut defence and inflammation Gut, 61 (12) (2012), pp. 1765-1773

25 C. Ranasinghe, S. Trivedi, D.K. Wijesundara, et al.IL-4 and IL-13 receptors: roles in immunity and powerful vaccine adjuvants Cytokine Growth Factor Rev, 25 (4) (2014), pp. 437-442

26 A.C. Little, P. Pathanjeli, Z. Wu, et al.IL-4/IL-13 stimulated macrophages enhance breast cancer invasion via rho-GTPase regulation of synergistic VEGF/CCL-18 signaling Front Oncol, 9 (2019), p. 456

27 S. Nicola, I. Ridolfi, G. Rolla, et al.IL-17 promotes nitric oxide production in non-small-cell lung cancer J Clin Med, 10 (19) (2021), p. 4572

28 J. Shi, X. Song, B. Traub, et al.Involvement of IL-4, IL-13 and their receptors in pancreatic cancer Int J Mol Sci, 22 (6) (2021), p. 2998

29 B. Szymanska, E. Sawicka, K. Jurkowska, et al.The relationship between interleukin-13 and angiogenin in patients with bladder cancer J Physiol Pharmacol, 72 (4) (2021), pp. 615-622

30 T. Shimamura, S.R. Husain, R.K. PuriThe IL-4 and IL-13 pseudomonas exotoxins: new hope for brain tumor therapy Neurosurg Focus, 20 (4) (2006), p. E11

31 H. Jiang, M.B. Harris, P. RothmanIL-4/IL-13 signaling beyond JAK/STAT J Allergy Clin Immunol, 105 (6) (2000), pp. 1063-1070

32 E.P. Karmele, T.S. Pasricha, T.R. Ramalingam, et al.Anti-IL-13Rα2 therapy promotes recovery in a murine model of inflammatory bowel disease Mucosal Immunol, 12 (5) (2019), pp. 1174-1186

33 C.W.S. Ko, R.J. Cuthbert, N.M. Orsi, et al.Lack of interleukin-4 receptor alpha chain-dependent signalling promotes azoxymethane-induced colorectal aberrant crypt focus formation in Balb/c mice J Pathol, 214 (5) (2008), pp. 603-609

34 R. Barderas, R.A. Bartolomé, M.J. Fernandez-Aceñero, et al.High expression of IL-13 receptor α2 in colorectal cancer is associated with invasion, liver metastasis, and poor prognosis Cancer Res, 72 (11) (2012), pp. 2780-2790

35 T. Huang, X. Song, Y. Yang, et al.Autophagy and hallmarks of cancer Crit Rev Oncog, 23 (5–6) (2018), pp. 247-267

36 X. Huang, G. Gan, X. Wang, et al.The HGF-MET axis coordinates liver cancer metabolism and autophagy for chemotherapeutic resistance Autophagy, 15 (7) (2019), pp. 1258-1279

37 Y.F. Peng, Y.H. Shi, Z.B. Ding, et al.Autophagy inhibition suppresses pulmonary metastasis of HCC in mice via impairing anoikis resistance and colonization of HCC cells Autophagy, 9 (12) (2013), pp. 2056-2068

38 M.C. Yang, H.C. Wang, Y.C. Hou, et al.Blockade of autophagy reduces pancreatic cancer stem cell activity and potentiates the tumoricidal effect of gemcitabine Mol Cancer, 14 (2015), p. 179

39 H. Liu, Z. He, T. von Rütte, et al.Down-regulation of autophagy-related protein 5 (ATG5) contributes to the pathogenesis of early-stage cutaneous melanoma Sci Transl Med, 5 (202) (2013), p. 202ra123

40 L.A. Donehower, T. Soussi, A. Korkut, et al.Integrated analysis of TP53 gene and pathway alterations in the cancer genome atlas Cell Rep, 28 (5) (2019), pp. 1370-1384 e5

41 T. Baslan, J.P. Morris 4th, Z. Zhao, et al.Ordered and deterministic cancer genome evolution after p53 loss Nature, 608 (7924) (2022), pp. 795-802

42 E. Morselli, S. Shen, C. Ruckenstuhl, et al.p53 inhibits autophagy by interacting with the human ortholog of yeast Atg17, RB1CC1/FIP200 Cell Cycle, 10 (16) (2011), pp. 2763-2769

43 K.M. Livesey, R. Kang, P. Vernon, et al.p53/HMGB1 complexes regulate autophagy and apoptosis Cancer Res, 72 (8) (2012), pp. 1996-2005

44 N. Allende-Vega, M.K. SavilleTargeting the ubiquitin–proteasome system to activate wild-type p53 for cancer therapy Semin Cancer Biol, 20 (1) (2010), pp. 29-39

查看原文

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

FGF21-mediated autophagy: Remodeling the homeostasis in response to stress in liver diseases

Autophagy-related lncRNAs in tumor progression and drug resistance: A double-edged sword

Potential relationship between autophagy and ferroptosis in myocardial ischemia/reperfusion injury

Molecular basis of fluoride toxicities: Beyond benefits and implications in human disorders

Progranulin regulation of autophagy contributes to its chondroprotective effect in osteoarthritis

Related Author

Wei Shen

Modan Yang

Hao Chen

Chiyu He

Huigang Li

Xinyu Yang

Jianyong Zhuo

Zuyuan Lin

Related Institution

Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine

The Institute for Organ Repair and Regenerative Medicine of Hangzhou

Institute of Organ Transplantation, Zhejiang University

Zhejiang University School of Medicine

National Center for Healthcare Quality Management in Liver Transplant

⁰