Insights Into Metastasis

Insights Into Metastasis

Cancer stem cells generate and sustain tumors, leading to tumor recurrence and metastasis. The cell cycle inhibitor p21CIP1 (p21) is a protein that plays a well-known role in halting cellular proliferation. But in previous work, Rachel B. Hazan, Ph.D.,  and colleagues have shown that p21 also exerts pro-metastatic effects in mammary tumor models via an unknown mechanism. Their paper, which published on July 1 in Molecular Cancer Research demonstrated that p21 expression activates Wnt signaling, a key signaling pathway known to be dysregulated in many types of cancer. Knocking out p21 in the PyMT mouse model of breast cancer suppressed Wnt signaling. p21 was found to turn on Wnt signaling by increasing levels of the transcription factor TCF1 and Cyclin D1, proteins that are important activators of Wnt signaling. The findings imply that targeting p21 in combination with chemotherapy might be an effective therapy against metastasis. Dr. Hazan is professor of pathology at Einstein.