Alternagin-C, an alpha2beta1 integrin ligand, attenuates collagen-based adhesion, stimulating the metastasis suppressor 1 expression in triple-negative breast tumor cells
0301 basic medicine
Integrins
Disintegrins
Microfilament Proteins
Triple Negative Breast Neoplasms
Ligands
Neoplasm Proteins
3. Good health
03 medical and health sciences
Cell Adhesion
Tumor Microenvironment
Humans
Collagen
Integrin alpha2beta1
DOI:
10.1016/j.toxicon.2022.02.001
Publication Date:
2022-02-09T01:29:59Z
AUTHORS (5)
ABSTRACT
Triple-negative breast cancer has an aggressive clinical course and its treatment has been challenging due to high metastatic risk. Molecular targets have been sought to provide better strategies for this type of cancer. Integrins are cell adhesion receptors involved in tumor progression and α2β1 integrin, a collagen receptor, has a key role in breast metastasis. Disintegrins, a family of proteins from snake venoms, selectively block the function of integrin receptors. Alternagin-C (ALT-C), a disintegrin-like protein purified from Bothrops alternatus venom, binds to α2β1 integrin, attenuating inflammation and angiogenesis, and decreasing metalloprotease levels in the tumor microenvironment, which suggests anti-metastatic effects. However, its mechanisms of action in metastatic tumor cells have not been fully explored. Here, we investigated ALT-C effects in a triple-negative breast cancer cell line (MDA-MB-231) to elucidate how α2β1 integrin affects cellular adhesion, migration and gene expression related to metastasis. We observed that ALT-C attenuated cell adhesion of MDA-MB-231 cells to collagen I. α2 integrin subunit silencing in MDA-MB-231 cells did not inhibit cell adhesion and migration to collagen I, indicating that other integrins play a crucial role in cell motility for this cell line. ALT-C also stimulated the metastasis suppressor 1 (MTSS1) expression and decreased metalloproteases MMP9 and MMP2. Therefore, we suggest that ALT-C contributes to impair metastasis, preventing extracellular matrix degradation and tumor attachment to collagen I, increasing MTSS1. This study is the first to elucidate the anti-metastatic mechanism involving a disintegrin-like protein from snake venom targeting α2β1 integrin and stimulating a metastasis suppressor.
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