Researchers at Brazil’s Federal University of São Paulo (UNIFESP) have identified a molecule on the cell surface that could be a promising therapeutic target for cancer. This molecule plays an important role in tumor progression by regulating cell behavior.
This FAPESP-supported study showed that overexpression of the Sindecam-4 (SDC4) receptor provides a protective shield to tumor cells. In laboratory experiments, the researchers silenced the receptor, halting the accelerated growth of tumor cells and causing them to resume responding to their naturally programmed cell death mechanisms.
This study also received financial support from the National Council for Scientific and Technological Development (CNPq), the Coordination Agency for the Improvement of Human Resources in Higher Education (CAPES), and the Brazilian Innovation Agency (FINEP).
“Our study shows that SDC4 may be a promising therapeutic target and serve as a diagnostic marker to monitor disease progression. Strategies to silence this molecule have the potential to prevent cancer cell proliferation, but We are still in the early stages of research and the results need to be validated in each specific case of the disease,” said Carla Cristina López, full professor at UNIFESP’s Faculty of Biological Sciences and lead author of the study published in the journal. Cell engineering.
Lopes explained that under normal conditions, cells express the SDC4 macromolecule for essential functions such as signal transduction and adhesion to other cells and tissues. However, changes in SDC4 expression, or when cells produce excessive amounts of the macromolecule, are associated with cancer development and progression. “Syndecum-4 protects tumor cells from a specific type of cell death called anoikis, which occurs when cells detach from tissue,” explains Professor López.
She points out that for cells to form tissues, they must be fixed, or “adhered” to each other and to the extracellular matrix, a type of filler between cells. Therefore, when normal cells become detached from the tissue, a self-destructive mechanism called anoikis, a Greek word meaning “death by homelessness”, is activated.
However, in cancer this process is blocked, and the most aggressive tumor cells have the ability to survive and migrate through the bloodstream until they colonize other organs (metastasis).
“What is a metastasis? A metastasis is a tumor-forming cell that leaves a tissue, enters the bloodstream, and invades other tissues. This happens because these cells manage to avoid anoikis, a form of cell death caused by loss of adhesion to the matrix,” the researchers explain.
In experiments conducted on adherent rabbit aortic endothelial cells cultured in a laboratory setting, the researchers observed that less than 5% of cells survived disruption of adhesion and remained alive in suspension. However, this small group became highly aggressive and showed overexpression of SDC4. But when researchers used genetic engineering techniques to silence the molecule, the cells lost their malignant properties and once again became dependent on adhesion for survival.
This reversal significantly increased programmed cell death and reduced the cells’ ability to invade, making SDC4 a promising therapeutic target for stopping metastasis before it begins. ”
Carla Cristina López, Full Professor, Faculty of Biological Sciences, UNIFESP
This study also showed that the mechanism of action of SDC4 involves regulation from early stages of the cell cycle. “When we silenced SDC4, the inhibitor of cell division increased (p27) acts early in the cell division process (G1 period) by blocking uncontrolled growth. Additionally, cyclin and CDK expression was also regulated (cyclin dependent kinase), these are regulators of cell cycle progression,” the researchers said.
Research into the role of SDC4 in cell cycle regulation was supported by FAPESP and culminated in the master’s thesis of scholarship recipient Bianca Zaia F. Ferreira.
After describing the role of SDC4 in tumor cell survival and aggressiveness, UNIFESP researchers are now investigating whether cannabidiol (CBD) can act on SDC4 molecules. “The discovery of the role of SDC4 in metastasis paves the way for a series of new studies. One of our lines of research is to test whether cannabidiol can reverse the malignant behavior of anoikis-resistant cells by regulating SDC4 expression or by interfering with the signaling pathways that sustain uncontrolled proliferation. This would be an interesting approach, but we are still in the early stages of research,” she says.
sauce:
São Paulo Research Foundation (FAPESP)
Reference magazines:
Ferreira, BZF, Others. (2026). SDC4 silencing promotes cell cycle arrest at the restriction point (R point) in anoikis-resistant endothelial cells. Cell engineering. DOI: 10.1007/s10616-026-00931-x. https://link.springer.com/article/10.1007/s10616-026-00931-x
