LATS Enzymes Balance Cell Fate in Breast Tissue

Study provides better understanding of why some cancers are resistant to therapy.

Investigators have identified a key enzyme that influences the treatment and development of breast cancer.

A study published in Nature focused on cancer-inhibiting genes that prevent normal cells from becoming cancerous. In particular, the investigators examined the tumor suppressors LATS1 and LATS2.

When LATS is depleted, it changes the processes in the breast tissue, causing the number of luminal precursor cells in the epithelial tissue of the breast glands to increase. According to the study, these cells are the origin of most types of breast cancer in humans.

“LATS balances cell fate in the breast tissue,” said lead investigator Mohamed Bentires-Alj. “In its absence, the equilibrium shifts and more cells that can give rise to tumors develop.”

When the breast tissue is healthy, the LATS bring together the estrogen receptor alpha with the protein degradation machinery. However, when LATS is depleted, the receptor can no longer be properly degraded, which causes issues for cancer therapy.

“We were able to show that cancer cells without LATS no longer respond to Fluvestrant, an estrogen-receptor antagonist that promotes its degradation. They were resistant,” Bentires-Alj said.

Additional findings showed the removal of LATS stabilized the proteins YAP and TAZ, which are upregulated in numerous cancers, and boosts cell proliferation, according to the study.

“Thanks to our newly gained insights into the molecular processes in healthy breast tissue, we now also better understand how cells of origin of cancer expand and why certain tumors are resistant to therapy,” Bentires-Alj concluded.