Research reveals new functions of two proteins for cell function and renewal

Two recently published studies led by Brazilian scientists reveal the key roles of multifunctional proteins, STIP1 and Maspin, in vital cellular processes.

The results demonstrate new protein functions that help clarify how cells maintain their shape, communicate, and renew themselves. These findings contribute to new studies on cancer, embryogenesis, and potential applications in regenerative medicine.

According to one of the studies, STIP1 plays a central role in embryonic development and maintaining pluripotency, or the ability of cells to multiply and give rise to other cell types.  

STIP1 (Stress Inducible Protein 1) is present in the body from the earliest stages of life and is considered essential for maintaining protein balance within cells (homeostasis). It acts as a bridge, helping other proteins called molecular chaperones interact and transfer their “cargo,” or client proteins, for processing. 

The other study showed that Maspin acts on cell morphology, as a cytoskeleton regulator, and epithelial adhesion. Scientific literature describes the protein as a tumor suppressor due to its role in preventing disease progression and spread in the body. Therefore, it is an important target related to cancer, especially breast cancer.  

Both articles were published in the same issue of the Nature group’s Communications Biology journal, under the coordination of scientists from the Department of Cellular and Developmental Biology at the Biomedical Sciences Institute of the University of São Paulo (ICB-USP). 

“Our work is focused on basic research, a path that requires time, dedication, and continuity until the results are consolidated. Many students and researchers participate in this journey, and each one leaves their mark on the advancement of knowledge. Seeing this collective effort turn into a publication is extremely gratifying. It’s the certainty that we’re contributing to the construction of science,” Professor Marilene Hohmuth Lopes of ICB-USP and coordinator of the study on STIP1 told Agência FAPESP.

Professor Nathalie Cella, also from ICB-USP and the corresponding author of the article on Maspin, highlights the importance of investing in long-term research. “Advances like these only happen with continuous investment in basic science and the training of young researchers,” she says.

‘Guardian of pluripotency’

Using genetically modified mice, Lopes’s group of scientists discovered that STIP1 is essential for maintaining stem cells in their primitive state — the state in which they can transform into any type of tissue.  

The scientists found that a decrease in the protein led to a loss of pluripotency when analyzing murine embryonic stem cells. The cells also became more vulnerable to stress and exhibited genetic instability.

Increasing the protein had the opposite effect: more growth, resistance, and maintenance of stem cell identity.  

The result of the doctoral thesis of Camila Felix de Lima Fernandes, who received a scholarship from FAPESP, the study demonstrated that STIP1 is indispensable for embryonic development, controlling genomic stability, cell survival, and the expression of pluripotency genes. This paves the way for the search for strategies in regenerative medicine.

This branch of medicine, which emerged in the late 1990s, seeks ways to recover and regenerate tissues, organs, and other structures in the human body that have been damaged due to trauma or disease. “We discovered that STIP1 acts as a kind of guardian of stem cells, ensuring that cellular machinery functions accurately during the most delicate stages of life,” says Lopes.

Versatility

In the case of Maspin, the researchers discovered that the protein directly supports the cell. It binds to internal structures that give cells their shape and stability.  

The group used a combination of proteomic approaches, functional analyses, and imaging. They found that reducing the presence of Maspin in cells that line body surfaces (epithelial cells) causes them to lose contact with each other and change shape.  

The research also showed that the protein controls the growth of filaments that organize the interior of cells. In this way, it functions as a kind of structural organizer that ensures tissue integrity.

The result of the doctoral research of student Luiz Eduardo da Silva, which began shortly before the COVID-19 pandemic in 2020, the study helps explain why Maspin can play opposite roles depending on the cellular context, functioning as either a protector or a promoter of cancer.

“Our journey with Maspin shows how basic science, when guided by curiosity and persistence, can reveal new aspects of already known proteins and redefine established concepts,” adds Cella, explaining that she “inherited” her interest in the protein more than 20 years ago when she did her postdoctoral research in Professor Ming Zhang’s laboratory at Baylor College of Medicine in the United States.

FAPESP also supported the studies through scholarships and research grants (21/12268-4, 18/15553-9, 23/08391-0, 21/13114-0, 19/06971-4, 21/13070-3, 20/05443-1, 22/14445-3, 14/17385-5, 19/14952-0, 21/05287-2, 22/08106-1, 20/10671-3, 19/12710-9, 17/26158-0, 18/14933-2, 11/13906-2, 18/15557-4, and 19/00341-9). 

About São Paulo Research Foundation (FAPESP)
The São Paulo Research Foundation (FAPESP) is a public institution with the mission of supporting scientific research in all fields of knowledge by awarding scholarships, fellowships and grants to investigators linked with higher education and research institutions in the State of São Paulo, Brazil. FAPESP is aware that the very best research can only be done by working with the best researchers internationally. Therefore, it has established partnerships with funding agencies, higher education, private companies, and research organizations in other countries known for the quality of their research and has been encouraging scientists funded by its grants to further develop their international collaboration. You can learn more about FAPESP at www.fapesp.br/en and visit FAPESP news agency at www.agencia.fapesp.br/en to keep updated with the latest scientific breakthroughs FAPESP helps achieve through its many programs, awards and research centers. You may also subscribe to FAPESP news agency at http://agencia.fapesp.br/subscribe.