Contact Us

SMAD7 Sustains XIAP Expression and Migration of Colorectal Carcinoma Cells

Affiliations
  • 1Department of Systems Medicine, University of Rome “Tor Vergata”, 00133 Rome, Italy.
  • 2Department of Biomedicine and Prevention, University of Rome “Tor Vergata”, 00133 Rome, Italy.
  • 3Department of Biology, Laboratorio di Biologia Delle Cellule Staminali, University of Naples Federico II, 80126 Naples, Italy.
  • 4Laboratory of Preclinical and Translational Research, Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), 85028 Rionero in Vulture, Italy.
  • 5Gastroenterology Unit, Fondazione Policlinico “Tor Vergata”, 00133 Rome, Italy.

Published on:

July 13, 2024

Abstract

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, mRNA correlated with expression. Our data show that positively regulates expression and migration of CRC cells, and suggest a mechanism by which SMAD7 controls the architecture components of the CRC cell cytoskeleton.

Keywords:

Related Concept Videos

JoVE Research Video for Role Of Notch Signalling In Intestinal Stem Cell Renewal 01:12

2.0K

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also…

JoVE Research Video for Abnormal Proliferation 02:23

4.2K

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the…

JoVE Research Video for Cancer Cell Migration through Invadopodia 01:35

2.2K

Invadosome is a broad category of cell surface structures with proteolytic activity that  degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However,…

JoVE Research Video for mTOR Signaling and Cancer Progression 03:03

3.5K

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the…

JoVE Research Video for The JAK-STAT Signaling Pathway 01:20

7.9K

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2…

JoVE Research Video for TGF - β Signaling Pathway 01:16

6.9K

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors…