MSK1 Levels Associated With Relapse, Metastasis in ER-positive Breast Cancer

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Researchers found that MSK1 is a key regulator of latency.
Researchers found that MSK1 is a key regulator of latency.

Downregulation of mitogen- and stress-activated protein kinase-1 (MSK1) leads to decreased differentiation of tumor cells and contributes to early relapse and bone metastases among patients with estrogen receptor (ER)-positive breast cancer, according to a study published in Nature Cell Biology.1

For this study, investigators performed a genome-wide short hairpin RNA (RshRNA) screening in mouse models to identify genes involved in breast cancer latency. Human ER-positive breast cancer cells were injected into mice, which formed latent micrometastatic bone lesions that eventually progressed to overt metastases; researchers found that MSK1 was a key regulator of latency.

To confirm these findings, the authors studied samples from patients with ER-positive breast cancer. Patients with bone relapse within 5 years after initial diagnosis had significantly downregulated levels of MSK1 (hazard ratio [HR], 0.41; P = .01); low levels of MSK1 correlated with low rates of metastasis-free survival (HR, 0.48; P = .01).

No differences in MSK1 expression were observed among patients with ER-negative breast cancer.

MSK1 depletion not only led to increased bone homing by cancerous cells, but an increased capacity for metastasis in dormant bone metastatic luminal breast cancer cells, suggesting that MSK1 is a regulator of dormancy.

The authors concluded that the “results indicated that MSK1 prevents metastatic progression of [ER-positive] breast cancer, suggesting that stratifying patients with breast cancer as high or low risk for early relapse based on MSK1 expression could improve prognosis.”

Reference

  1. Gawrzak S, Rinaldi L, Gregorio S, et al. MSK1 regulates luminal cell differentiation and metastatic dormancy in ER+ breast cancer. Nat Cell Biol. 2017 Jan 22. doi: 10.1038s41556-017-0021-z [Epub ahead of print]

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