Inhibition of Breast Cancer Cell Invasion by Ras Suppressor-1 (RSU-1) Silencing Is Reversed by Growth Differentiation Factor-15 (GDF-15)

• Published in: International journal of molecular sciences 2019-01, Vol.20 (1), p.163
• Main Authors: Gkretsi, Vasiliki, Louca, Maria, Stylianou, Andreas, Minadakis, George, Spyrou, George M, Stylianopoulos, Triantafyllos
• Format: Article
• Language: English
• Subjects: Actin; Actin Cytoskeleton - genetics; Actin Cytoskeleton - metabolism; Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Apoptosis; Binding; Breast cancer; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cdc42 protein; Cell adhesion & migration; Cell division; Clustering; Colorectal cancer; Cytokines; Cytokinesis; Cytoskeleton; Down-Regulation; Extracellular matrix; Female; Gelatinase A; Gene expression; Gene Silencing; Growth Differentiation Factor 15 - genetics; Growth Differentiation Factor 15 - metabolism; Growth Differentiation Factor 15 - pharmacology; Growth factors; GTP-binding protein; Guanine nucleotide-binding protein; Guanosine diphosphate; Hepatocellular carcinoma; Humans; Invasiveness; Kinases; LIM Domain Proteins - genetics; LIM Domain Proteins - metabolism; Liver cancer; MCF-7 Cells; Medical prognosis; Membrane Proteins - genetics; Membrane Proteins - metabolism; Metastases; Metastasis; Microfilament Proteins - genetics; Microfilament Proteins - metabolism; Molecular machines; Morphology; Neoplasm Invasiveness - genetics; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Proteins; Remission; rho-Associated Kinases - genetics; RhoA protein; Spheroids; Survival; Transcription; Transcription Factors - genetics; Transcription Factors - metabolism
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20010163

Extracellular matrix (ECM)-related adhesion proteins are important in metastasis. Ras suppressor-1 (RSU-1), a suppressor of -transformation, is localized to cell⁻ECM adhesions where it interacts with the Particularly Interesting New Cysteine-Histidine rich protein (PINCH-1), being connected to Integrin Linked Kinase (ILK) and alpha-parvin (PARVA), a direct actin-binding protein. was also found upregulated in metastatic breast cancer (BC) samples and was recently demonstrated to have metastasis-promoting properties. In the present study, we transiently silenced in BC cells, MCF-7 and MDA-MB-231. We found that silencing leads to downregulation of Growth Differentiation Factor-15 ( ), which has been associated with both actin cytoskeleton reorganization and metastasis. silencing also reduced the mRNA expression of and cell division control protein-42 ( ), while increasing that of and regardless of the presence of GDF-15. However, the downregulation of actin-modulating genes , , Rho associated kinase-1 ( ), and following depletion was completely reversed by GDF-15 treatment in both cell lines. Moreover, complete rescue of the inhibitory effect of silencing on cell invasion was achieved by GDF-15 treatment, which also correlated with matrix metalloproteinase-2 expression. Finally, using a graph clustering approach, we corroborated our findings. This is the first study providing evidence of a functional association between and with regard to cancer cell invasion.