SMAD7 Sustains XIAP Expression and Migration of Colorectal Carcinoma Cells.
Marco ColellaAndrea IannucciClaudia MarescaFrancesco AlbanoCarmela MazzoccoliFederica LaudisiIvan MonteleoneGiovanni MonteleonePublished in: Cancers (2024)
The reorganization of the cell cytoskeleton and changes in the content of cell adhesion molecules are crucial during the metastatic spread of tumor cells. Colorectal cancer (CRC) cells express high SMAD7, a protein involved in the control of CRC cell growth. In the present study, we evaluated whether SMAD7 regulates the cytoskeleton reorganization and dynamics in CRC. Knockdown of SMAD7 with a specific antisense oligonucleotide (AS) in HCT116 and DLD1, two human CRC cell lines, reduced the migration rate and the content of F-ACTIN filaments. A gene array, real-time PCR, and Western blotting of SMAD7 AS-treated cells showed a marked down-regulation of the X-linked inhibitor of apoptosis protein (XIAP), a member of the inhibitor of apoptosis family, which has been implicated in cancer cell migration. IL-6 and IL-22, two cytokines that activate STAT3, enhanced XIAP in cancer cells, and such induction was attenuated in SMAD7-deficient cells. Finally, in human CRC, SMAD7 mRNA correlated with XIAP expression. Our data show that SMAD7 positively regulates XIAP expression and migration of CRC cells, and suggest a mechanism by which SMAD7 controls the architecture components of the CRC cell cytoskeleton.
Keyphrases
- cell cycle arrest
- epithelial mesenchymal transition
- transforming growth factor
- induced apoptosis
- cell death
- endoplasmic reticulum stress
- pi k akt
- cell migration
- endothelial cells
- signaling pathway
- binding protein
- small cell lung cancer
- squamous cell carcinoma
- stem cells
- single cell
- cell proliferation
- dna methylation
- gene expression
- cell therapy
- high resolution
- cell adhesion
- young adults
- deep learning
- mass spectrometry
- bone marrow
- protein protein
- nucleic acid