When it comes to cancer metastasis, it takes two to tango. That was one of the key findings of a new study led by researchers at Memorial Sloan Kettering Cancer Center (MSK): The TGF-beta and RAS signaling pathways work together to spur the spread of cancer in lung adenocarcinoma, a leading cause of cancer deaths around the world.
Memorial Sloan Kettering Cancer CenterSep 6 2024 When it comes to cancer metastasis, it takes two to tango. That was one of the key findings of a new study led by researchers at Memorial Sloan Kettering Cancer Center : The TGF-beta and RAS signaling pathways work together to spur the spread of cancer in lung adenocarcinoma, a leading cause of cancer deaths around the world.
"About 9 in 10 deaths from cancer are caused by metastasis," says Jun Ho Lee, PhD, the study's first author and a postdoctoral researcher in the lab of senior study author Joan Massagué, PhD. "So research to understand, prevent, and treat metastasis has great potential to improve the lives of many people."
Here, the researchers determined that a transcription factor that is controlled by RAS plays a critical role in metastasis. It's known as RAS response element binding protein 1 . They found that RREB1 collaborates with a signaling complex called SMAD4, which is controlled by TGF-beta. And inhibiting RREB1 disabled the metastatic process in mouse models, suggesting it could be a potential new drug target -; both in lung cancer and in related diseases like lung fibrosis.
We know that the TGF-beta pathway promotes injury repair and suppresses the formation of tumors in healthy tissues, but when tumors manage to grow, it promotes metastasis. So this is a big question we wanted to understand: How is it that metastasis can take something that is normally present to keep tissues healthy, turn it around, and use it to promote metastatic growth? And this has led to a whole program of research in my lab.
"So the biotech industry has been looking for ways to target TGF-beta only part-time or in restricted ways," he says. "Here we've discovered a new candidate for that type of intervention, only focused on a partner signal that we now know is also required for metastasis and fibrosis." "We can then expand these understandings to other tumor types, to other organs in the body where metastases develop, to other forms of fibrosis," he says.
Lung Cancer Metastasis Adenocarcinoma Cell Cytokine Embryonic Development Fibrosis Genes Mouse Model Protein Research Technology Tumor
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