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Tetraspanin-29 activates Notch signaling by interacting with ADAM10 to enhance its activity in colorectal cancer.
Yuan, Shijie; Yin, Yan; Wang, Kuansong; Zhou, Haiyan; Qian, Cheng.
Afiliación
  • Yuan S; Xiehe Stem Cell Genetic Engineering Co. Ltd., East China Center, No. 988 Tianheng Road, Huzhou, Zhejiang 313000, China.
  • Yin Y; Department of Colon-rectal Surgery, Huzhou Maternity & Child Health Care Hospital, No. 2 East Street, Huzhou, Zhejiang 313000, China.
  • Wang K; Department of Pathology, Xiangya Medical College, Central South University, No. 172 Tongzipo Road, Changsha, Hunan 410003, China.
  • Zhou H; Department of Pathology, Xiangya Medical College, Central South University, No. 172 Tongzipo Road, Changsha, Hunan 410003, China.
  • Qian C; Department of Colon-rectal Surgery, Huzhou Maternity & Child Health Care Hospital, No. 2 East Street, Huzhou, Zhejiang 313000, China.
Biochem Cell Biol ; 100(4): 292-300, 2022 08 01.
Article en En | MEDLINE | ID: mdl-35968819
ABSTRACT
ADAM10 acts upstream of Notch signaling and plays oncogenic roles in various cancers. Tetraspanin family proteins regulate ADAM10 trafficking and activity. Here, we aimed to investigate whether and how tetraspanin-29 modulates ADAM10 in colorectal cancer (CRC). We found that ADAM10 expression was upregulated in CRC tissues and this was cross-validated in the TCGA COAD data set. The ADAM10 protein level and its α-secretase activity were enhanced in CRC cell lines compared with control cell lines. Co-immunoprecipitation showed ADAM10 interacted with tetraspanin-29 in the LoVo cell line. Tetraspanin-29 knockdown reduced the cell surface trafficking and α-secretase activity of ADAM10. In addition, tetraspanin-29 knockdown inhibited Notch activity in a luciferase reporter assay and reduced the levels of cleaved Notch1 and Notch target genes such as HES2, c-MYC, and cyclin D3. Consistently, tetraspanin-29 overexpression increased cleaved Notch1 and this effect was blocked by ADAM10 inhibitors. The TCGA COAD data set confirmed the positive correlations of tetraspanin-29 with HES2, c-MYC, and cyclin D3. Thus, the tetraspanin-29/ADAM10/Notch pathway plays an important role in CRC.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Neoplasias Colorrectales / Secretasas de la Proteína Precursora del Amiloide Límite: Humans Idioma: En Revista: Biochem Cell Biol Asunto de la revista: BIOQUIMICA Año: 2022 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Neoplasias Colorrectales / Secretasas de la Proteína Precursora del Amiloide Límite: Humans Idioma: En Revista: Biochem Cell Biol Asunto de la revista: BIOQUIMICA Año: 2022 Tipo del documento: Article País de afiliación: China