Reactome | Degradation of CDH1

Degradation of CDH1

Stable Identifier

R-HSA-9766229

Type

Pathway

Species

Homo sapiens

ReviewStatus

3/5

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Cell-Cell communication (Homo sapiens)

- Cell junction organization (Homo sapiens)
  - Cell-cell junction organization (Homo sapiens)
    - Adherens junctions interactions (Homo sapiens)
      - Regulation of Homotypic Cell-Cell Adhesion (Homo sapiens)
        
        Regulation of Expression and Function of Type I Classical Cadherins (Homo sapiens)
        
        Regulation of CDH1 Expression and Function (Homo sapiens)
        
        Regulation of CDH1 Function (Homo sapiens)
        
        Degradation of CDH1 (Homo sapiens)

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Early stages of epithelial-to-mesenchymal transition likely involve post-translational downregulation of CDH1, while later stages of EMT involve transcriptional silencing of CDH1 (Janda et al. 2006).

Two E3 ubiquitin ligases have been reported to ubiquitinate CDH1 and promote its degradation. MDM2 (HDM2) was reported to mediate ubiquitin-dependent degradation of CDH1 by the proteasome (Yang et al. 2006; Adhikary et al. 2014; Lu et al. 2015; Wang et al. 2020; Zhao et al. 2020), while CBLL1 (Hakai) was reported to mediated ubiquitin-dependent lysosomal degradation of CDH1 (Fujita et al. 2002; Shen et al. 2008; Chen et al. 2009; Hartsock and Nelson 2012; Smyth et al. 2012; Sako-Kubota et al. 2014; Lu et al. 2018; reviewed in Zhang et al. 2023).

Literature References

PubMed ID	Title	Journal	Year
31337857	Targeting cell membrane HDM2: A novel therapeutic approach for acute myeloid leukemia Wang, H, Zhao, D, Nguyen, LX, Wu, H, Li, L, Dong, D, Troadec, E, Zhu, Y, Hoang, DH, Stein, AS, Al Malki, M, Aldoss, I, Lin, A, Ghoda, LY, McDonald, T, Pichiorri, F, Carlesso, N, Kuo, YH, Zhang, B, Jin, J, Marcucci, G	Leukemia	2020
29356040	Basolateral CD147 induces hepatocyte polarity loss by E-cadherin ubiquitination and degradation in hepatocellular carcinoma progress Lu, M, Wu, J, Hao, ZW, Shang, YK, Xu, J, Nan, G, Li, X, Chen, ZN, Bian, H	Hepatology	2018
18057010	Cdc42 regulates E-cadherin ubiquitination and degradation through an epidermal growth factor receptor to Src-mediated pathway Shen, Y, Hirsch, DS, Sasiela, CA, Wu, WJ	J Biol Chem	2008
38045551	Dynamics and functions of E-cadherin complexes in epithelial cell and tissue morphogenesis Zhang, N, Häring, M, Wolf, F, Großhans, J, Kong, D	Mar Life Sci Technol	2023
22715382	Reduced surface expression of epithelial E-cadherin evoked by interferon-gamma is Fyn kinase-dependent Smyth, D, Leung, G, Fernando, M, McKay, DM	PLoS One	2012
22693575	Competitive regulation of E-cadherin juxtamembrane domain degradation by p120-catenin binding and Hakai-mediated ubiquitination Hartsock, A, Nelson, WJ	PLoS One	2012
25086032	Inhibition of epithelial to mesenchymal transition by E-cadherin up-regulation via repression of slug transcription and inhibition of E-cadherin degradation: dual role of scaffold/matrix attachment region-binding protein 1 (SMAR1) in breast cancer cells Adhikary, A, Chakraborty, S, Mazumdar, M, Ghosh, S, Mukherjee, S, Manna, A, Mohanty, S, Nakka, KK, Joshi, S, De, A, Chattopadhyay, S, Sa, G, Das, T	J Biol Chem	2014
25253721	Minus end-directed motor KIFC3 suppresses E-cadherin degradation by recruiting USP47 to adherens junctions Sako-Kubota, K, Tanaka, N, Nagae, S, Meng, W, Takeichi, M	Mol Biol Cell	2014
26280083	MTBP Promotes the Invasion and Metastasis of Hepatocellular Carcinoma by Enhancing the MDM2-Mediated Degradation of E-Cadherin Lu, S, Zhou, W, Wei, H, He, L, Li, L	Dig Dis Sci	2015
16751808	Raf plus TGFbeta-dependent EMT is initiated by endocytosis and lysosomal degradation of E-cadherin Janda, E, Nevolo, M, Lehmann, K, Downward, J, Beug, H, Grieco, M	Oncogene	2006
11836526	Hakai, a c-Cbl-like protein, ubiquitinates and induces endocytosis of the E-cadherin complex Fujita, Y, Krause, G, Scheffner, M, Zechner, D, Leddy, HE, Behrens, J, Sommer, T, Birchmeier, W	Nat. Cell Biol.	2002
32805084	LncRNA UCA1 maintains the low-tumorigenic and nonmetastatic status by stabilizing E-cadherin in primary prostate cancer cells Zhao, X, Wang, Y, He, J, Deng, R, Huang, X, Guo, Y, Li, L, Xie, R, Yu, J	Mol Carcinog	2020
16980628	MDM2 promotes cell motility and invasiveness by regulating E-cadherin degradation Yang, JY, Zong, CS, Xia, W, Wei, Y, Ali-Seyed, M, Li, Z, Broglio, K, Berry, DA, Hung, MC	Mol Cell Biol	2006
19711372	An acidic extracellular pH disrupts adherens junctions in HepG2 cells by Src kinases-dependent modification of E-cadherin Chen, Y, Chen, CH, Tung, PY, Huang, SH, Wang, SM	J Cell Biochem	2009