Targeting stem cell signaling could halt liver cancer progression Elucidating a new therapeutic target



Kanazawa, Japan – Stem cells from liver cancer, believed to be responsible for the malignant traits of HCC, are considered the target to be eradicated. Today, Japanese researchers have discovered a signaling pathway in HCC that promotes the properties of liver cancer stem cells.

In a study published last month in Molecular Oncology, researchers at the University of Kanazawa found that signaling of bone morphological protein 9 (BMP9) promotes the properties of liver cancer stem cells by enhancing the expression of l DNA binding protein 1 (ID1) inhibitor.

BMP9 is a known player in liver disease because it prevents the death of liver cancer cells, encourages their proliferation and promotes tumor formation in the liver. The Kanazawa University team set out to determine whether BMP9 specifically plays an important role in activating liver cancer stem cells, a minority subset of cancer cells that can lead to tumor initiation, promote tumor progression and induce drug resistance.

“Cancer stem cells are thought to be responsible for the malignant characteristics of cancer such as tumor progression, recurrence, metastasis and drug resistance,” says lead study author Han Chen. “Because BMP9 has recently been associated with the progression of liver cancer, we wanted to study the interaction between BMP9 and cancer stem cells in HCC. “

To do this, the researchers examined the expression of BMP9 in tumor tissue samples from patients with HCC and analyzed the correlation with patient prognosis and expression of the liver cancer strain marker EpCAM.

“The results were very interesting,” says Kouki Nio, corresponding author. “We found that high BMP9 HCC cases had lower overall survival. In addition, expression of BMP9 correlated with expression of EpCAM in HCC tissues. These suggest that BMP9 is linked to the malignant potential of HCC.

In fact, BMP9 promoted the expression of EpCAM by regulating the expression of ID1 in HCC cells. Blockade of BMP9-ID1 signaling by BMP receptor inhibitors successfully suppressed HCC tumor growth and EpCAM expression in mice.

“Our results suggest that BMP9-ID1 signaling is crucial for the activation of liver cancer stem cells. As such, targeting this signaling could be a promising therapy for patients with advanced HCC in the future, ”says Chen.

In terms of future application for patients with HCC, certain clinical studies using BMP receptor inhibitor monotherapy or in combination with other agents are desired.


This work was supported by JSPS KAKENHI Grant Numbers JP18K15807 and JP20K17044.


Title: MP9-ID1 Signaling Promotes Properties of EpCAM-Positive Cancer Stem Cells in Hepatocellular Carcinoma

Journal: Molecular oncology

Authors: Han Chen, Kouki Nio, Taro Yamashita, Hikari Okada, Ru Li, Tsuyoshi Suda, Yingyi Li, Phuong Thi Bich Doan, Akihiro Seki, Hidetoshi Nakagawa, Tadashi Toyama, Takeshi Terashima, Noriho Iida, Tetsuro Shimakuchi, Kawagime Takator , Yoshio Sakai, Tatsuya Yamashita, Eishiro Mizukoshi, Masao Honda, Shuichi Kaneko


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