Newly characterized motile sperm domain‐containing protein 2 promotes human breast cancer metastasis

• Published in: International journal of cancer 2019-01, Vol.144 (1), p.125-135
• Main Authors: Salem, Yaniv, Yacov, Niva, Propheta‐Meiran, Oshrat, Breitbart, Eyal, Mendel, Itzhak
• Format: Article
• Language: English
• Subjects: Animals; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cancer; Cell adhesion & migration; Cell Line, Tumor; Cell Movement; Chemotaxis; Female; Humans; Immunohistochemistry; Invasiveness; Leukocyte migration; Lung - metabolism; Lung - pathology; Medical research; Membrane proteins; Membrane Proteins - genetics; Membrane Proteins - metabolism; Metastases; Metastasis; Mice, SCID; migration; Molecular Cancer Biology; Monocytes; MOSPD2; Neoplasm Metastasis; Phosphorylation; Proteins; Receptors, Chemokine - genetics; Receptors, Chemokine - metabolism; RNA Interference; Tissue Array Analysis; Transplantation, Heterologous; Tumor cell lines; Tumors
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.31665

Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among women worldwide. Breast cancer metastasis results in poor prognosis and increased mortality, but the mechanisms of breast cancer metastasis are yet to be fully resolved. Identifying distinctive proteins that regulate metastasis might be targeted to improve therapy in breast cancer. We previously described MOSPD2 as a surface membrane protein that regulates monocyte migration in vitro. In this study, we demonstrate for the first time that MOSPD2 has a major role in breast cancer cell migration and metastasis. MOSPD2 expression was highly elevated in invasive and metastatic breast cancer while it was absent or residual in normal tissue and in primary in situ tumors. In vitro experiments showed that silencing MOSPD2 in different breast cancer cell lines significantly inhibited cancer cell chemotaxis migration. Mechanistically, we found that silencing MOSPD2 profoundly abated phosphorylation events that are involved in breast tumor cell chemotaxis. In vivo, MOSPD2‐silenced breast cancer cells exhibited marked impaired metastasis to the lungs. These results indicate that MOSPD2 plays a key role in the migration and metastasis of breast cancer cells and may be used to prevent the spreading of breast cancer cells and to mediate their death. What's new? Motile sperm domain‐containing protein 2 (MOSPD2) is a key regulator of monocyte migration and is suspected of promoting cancer cell metastasis. In cancer patients, its expression is inversely correlated with survival. Here, MOSPD2 expression was found to be significantly elevated in metastatic breast cancer cells, with no or only residual expression in normal tissues and primary in situ tumors. in vitro MOSPD2 silencing inhibited breast cancer cell migration and impeded migration‐associated phosphorylation events. Its silencing in vivo impaired metastasis to the lungs, suggesting that MOSPD2 inhibition could be a useful therapeutic strategy for metastatic breast cancer in human patients.