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Kinectin1 depletion promotes EGFR degradation via the ubiquitin-proteosome system in cutaneous squamous cell carcinoma.
Ma, Ji; Ma, Shudong; Zhang, Ying; Shen, Yi; Huang, Lei; Lu, Tianhao; Wang, Lu; Wen, Yunhan; Ding, Zhenhua.
Afiliación
  • Ma J; Department of Radiation Medicine, Guangdong Provincial Key Laboratry of Tropical Disease Research, School of Public Health, Southern Medical University, 510515, Guangzhou, China.
  • Ma S; Department of Oncology, Nanfang Hospital, Southern Mediacal University, 510515, Guangzhou, China.
  • Zhang Y; Department of Radiation Medicine, Guangdong Provincial Key Laboratry of Tropical Disease Research, School of Public Health, Southern Medical University, 510515, Guangzhou, China.
  • Shen Y; Department of Radiation Medicine, Guangdong Provincial Key Laboratry of Tropical Disease Research, School of Public Health, Southern Medical University, 510515, Guangzhou, China.
  • Huang L; Department of Burn, Nanfang Hospital, Southern Mediacal University, 510515, Guangzhou, China.
  • Lu T; Department of Radiation Medicine, Guangdong Provincial Key Laboratry of Tropical Disease Research, School of Public Health, Southern Medical University, 510515, Guangzhou, China.
  • Wang L; Department of Radiation Medicine, Guangdong Provincial Key Laboratry of Tropical Disease Research, School of Public Health, Southern Medical University, 510515, Guangzhou, China.
  • Wen Y; Department of Radiation Medicine, Guangdong Provincial Key Laboratry of Tropical Disease Research, School of Public Health, Southern Medical University, 510515, Guangzhou, China.
  • Ding Z; Department of Radiation Medicine, Guangdong Provincial Key Laboratry of Tropical Disease Research, School of Public Health, Southern Medical University, 510515, Guangzhou, China. dingzh@smu.edu.cn.
Cell Death Dis ; 12(11): 995, 2021 10 23.
Article en En | MEDLINE | ID: mdl-34689164
Depletion of kinectin1 (KTN1) provides a potential strategy for inhibiting tumorigenesis of cutaneous squamous cell carcinoma (cSCC) via reduction of epidermal growth factor receptor (EGFR) protein levels. Yet, the underlying mechanisms of KTN1 remain obscure. In this study, we demonstrate that KTN1 knockdown induces EGFR degradation in cSCC cells by promoting the ubiquitin-proteasome system, and that this effect is tumor cell-specific. KTN1 knockdown increases the expression of CCDC40, PSMA1, and ADRM1 to mediate tumor suppressor functions in vivo and in vitro. Mechanistically, c-Myc directly binds to the promoter region of CCDC40 to trigger the CCDC40-ADRM1-UCH37 axis and promote EGFR deubiquitination. Furthermore, KTN1 depletion accelerates EGFR degradation by strengthening the competitive interaction between PSMA1 and ADRM1 to inhibit KTN1/ADRM1 interaction at residues Met1-Ala252. These results are supported by studies in mouse xenografts and human patient samples. Collectively, our findings provide novel mechanistic insight into KTN1 regulation of EGFR degradation in cSCC.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Cutáneas / Carcinoma de Células Escamosas / Ubiquitina / Complejo de la Endopetidasa Proteasomal / Receptores ErbB / Proteínas de la Membrana Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Cell Death Dis Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Cutáneas / Carcinoma de Células Escamosas / Ubiquitina / Complejo de la Endopetidasa Proteasomal / Receptores ErbB / Proteínas de la Membrana Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Cell Death Dis Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido