SMOC1 is a tenascin-C interacting protein over-expressed in brain tumors

Florence Brellier1, Sabrina Ruggiero, Daniela Zwolanek

  • 1Friedrich Miescher Institute for Biomedical Research, Novartis Research Foundation, Basel, Switzerland. florence.brellier@fmi.ch

Insights

Researchers identified SPARC-related modular calcium-binding protein 1 (SMOC1) as a novel interactor of tenascin-C, a protein overexpressed in many cancers. SMOC1 is also elevated in brain tumors and can modulate tenascin-C

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Tenascin-C is an extracellular matrix protein frequently overexpressed in various cancers.
  • Identifying tenascin-C interactors can reveal new insights into cancer biology and potential therapeutic targets.

Purpose of the Study:

  • To identify novel proteins that interact with tenascin-C.
  • To investigate the role of SPARC-related modular calcium-binding protein 1 (SMOC1) in cancer, particularly its interaction with tenascin-C and its expression levels in brain tumors.

Main Methods:

  • Affinity purification of secreted proteins using a tenascin-C column followed by mass spectrometry.
  • Co-immunoprecipitation and Surface Plasmon Resonance Spectroscopy to confirm and quantify tenascin-C and SMOC1 interaction.
  • Analysis of RNA profiling data and Western blot to assess SMOC1 expression in brain tumors.
  • Cell migration assays to evaluate the functional impact of SMOC1 on tenascin-C-mediated glioma cell behavior.

Main Results:

  • Mass spectrometry identified phosphoglycerate kinase 1, clusterin, fibronectin, SMOC1, and nidogen-2 as potential tenascin-C interactors.
  • The interaction between tenascin-C and SMOC1 was confirmed, with a K(D) of 2.59∗10(-9)M, sensitive to EDTA.
  • SMOC1 mRNA and protein levels were significantly increased in oligodendrogliomas, astrocytomas, and glioblastomas compared to normal brain tissue.
  • SMOC1 demonstrated the ability to counteract the chemo-attractive effect of tenascin-C on U87 glioma cells.

Conclusions:

  • SPARC-related modular calcium-binding protein 1 (SMOC1) is a novel cancer-associated protein that interacts with tenascin-C.
  • SMOC1 expression is elevated in brain tumors, suggesting a role in tumorigenesis.
  • SMOC1 may play a role in modulating cancer cell migration in response to tenascin-C.

Related Concept Videos

Tumor Progression02:07

Tumor Progression

Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Tumor Progression02:07

Tumor Progression

Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Cytoskeletal Accessory Proteins01:13

Cytoskeletal Accessory Proteins

The cytoskeleton is an essential cell component that plays several structural and functional roles. However, the filaments that make up the cytoskeleton cannot function independently and depend on the accessory or ancillary proteins to effectively carry out their function. Accessory proteins associate with cytoskeletal filaments and their monomers, aiding filament formation and function. They also help in the cross-communication among cytoskeletal filaments. Cytoskeletal accessory proteins are...
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...