Stathmin 1 (STMN1) is a protein found within the cells of various organisms, including humans. It is a phosphoprotein, meaning its activity can be regulated by the addition or removal of phosphate groups. STMN1 plays a role in numerous cellular processes, contributing to the overall health and function of cells.
What is Stathmin 1?
STMN1 is a small protein. It is found ubiquitously throughout the body, with particularly high expression during embryonic development and in adult cells that are actively proliferating, as well as in nervous tissue and testes. The protein primarily resides within the cytosol.
The overarching function of STMN1 involves regulating microtubules. These are dynamic, hollow protein cylinders composed of alpha and beta tubulin heterodimers. Microtubules serve as a cellular “skeleton,” providing structural support, facilitating intracellular transport, and enabling cell movement and division. STMN1’s interaction with these structures is central to maintaining cellular organization and enabling dynamic cellular processes.
Its Role in Cellular Processes
STMN1 influences normal cellular activities by modulating the dynamic behavior of microtubules, which constantly switch between assembly (polymerization) and disassembly (depolymerization). STMN1 promotes microtubule depolymerization by either directly acting on microtubule ends, leading to their breakdown, or by sequestering alpha/beta-tubulin heterodimers, thus preventing their assembly into new microtubules. This regulation is achieved through phosphorylation at specific serine sites, which reduces STMN1’s ability to bind tubulin and destabilize microtubules.
Control of microtubule dynamics by STMN1 is important for many cellular processes. During cell division, known as mitosis, STMN1’s activity is temporarily switched off by phosphorylation to allow microtubules to polymerize and form the mitotic spindle, a structure necessary for accurate chromosome segregation. STMN1 also contributes to cell migration, enabling cells to move and change shape, which is important for tissue development and repair. It plays a role in maintaining overall cell shape and organization.
Stathmin 1 and Disease
Dysregulation of STMN1 activity, either through overexpression or altered phosphorylation, can contribute to the development and progression of various diseases. Its overexpression is frequently observed in a broad range of human malignancies, including leukemia, lymphoma, neuroblastoma, and cancers of the ovary, prostate, breast, and lung. In these contexts, elevated STMN1 levels are often associated with aggressive tumor phenotypes and poor patient outcomes.
In cancer, increased STMN1 expression can promote uncontrolled cell proliferation by affecting the cell cycle. For instance, high STMN1 levels can lead to abnormal or absent mitotic spindle assembly, causing cells to arrest in early mitosis or cycle uncontrollably. STMN1 also plays a role in metastasis, the spread of cancer cells to other parts of the body, by enhancing cell motility and invasion. Its overexpression has been linked to increased lung metastasis and is associated with lymph node metastasis in various human cancers.
Beyond its role in promoting proliferation and metastasis, STMN1 overexpression can also contribute to drug resistance in cancer cells, particularly against microtubule-targeting chemotherapies like taxanes. This occurs because STMN1’s ability to destabilize microtubules can counteract the drug’s mechanism of action, which aims to stabilize or disrupt microtubules. While cancer is the primary focus, STMN1 has also been implicated in some neurological conditions; for example, its levels are increased in spinal muscular atrophy (SMA) and it has been linked to fear, anxiety, and cognitive processing.
Implications for Medicine
Understanding STMN1’s role offers promising avenues for medical applications. STMN1 shows potential as a biomarker for disease diagnosis and prognosis, particularly in various cancers. Elevated serum STMN1 levels have been identified as a promising diagnostic marker for squamous cell carcinoma (SCC). In hepatocellular carcinoma (HCC), STMN1 overexpression can distinguish cancerous from normal tissues and predict patient survival.
STMN1’s association with aggressive tumor characteristics, such as lymph node metastasis and advanced cancer stage, makes it a potential prognostic indicator. Researchers are also exploring STMN1 as a therapeutic target, especially in cancer treatment. Strategies aimed at modulating STMN1 activity have shown promise in reducing cancer cell proliferation, motility, and metastasis, while also inducing apoptosis. These interventions can also enhance the sensitivity of cancer cells to existing chemotherapies, offering a novel approach to overcome drug resistance.