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The stem cell niche is the dynamic microenvironment where stem cells reside. Inside these niches, the cells may remain undifferentiated, undergo high self-renewal, or become lineage-specific progenitors. Stem cells coexist with other niche cells, such as stromal cells. They also interact closely with the ECM. Cell-cell and cell-matrix communication occur via adhesion molecules or soluble factors that signal the stem cells and determine their fate. Stromal cells also provide survival signals to...
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Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
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Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
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A stem cell is an unspecialized cell that can divide without limit as needed and can, under specific conditions, differentiate into specialized cells.
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All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
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Cell surface GRP78 promotes stemness in normal and neoplastic cells.

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Cell surface GRP78 (sGRP78) is crucial for reprogramming and promotes functions in pluripotent and breast cancer cells. This protein marks a stem-like breast cancer cell population with higher metastatic potential.

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Area of Science:

  • Cellular Biology
  • Cancer Research
  • Stem Cell Biology

Background:

  • Metastatic cancers exhibit embryonic signatures, suggesting stem cell mechanisms drive aggressive disease.
  • Identifying and targeting cancer stem-like cells remains a significant challenge in oncology.
  • GRP78, a chaperone protein, is normally intracellular but found on the cell surface of embryonic stem cells and various cancers.

Purpose of the Study:

  • To investigate the role of cell surface GRP78 (sGRP78) in cellular reprogramming and cancer stemness.
  • To determine if sGRP78 marks a population of tumor-initiating cells (TICs) with metastatic potential in breast cancer.

Main Methods:

  • Utilized cellular reprogramming techniques to study GRP78.
  • Analyzed GRP78 expression on induced pluripotent stem cells (iPSCs) and breast cancer cells.
  • Investigated the functional role of sGRP78 in cellular functions and tumor initiation.
  • Assessed the enrichment of stemness genes and metastatic potential in sGRP78-positive breast cancer cells in vivo.

Main Results:

  • Cell surface GRP78 (sGRP78) is expressed on iPSCs and plays a role in reprogramming.
  • sGRP78 enhances cellular functions in both pluripotent cells and breast cancer cells.
  • Overexpression of GRP78 in breast cancer cells induces a CD24-/CD44+ tumor-initiating cell (TIC) population.
  • sGRP78-positive breast cancer cells are enriched for stemness genes and represent a subset of TICs.
  • sGRP78-positive breast cancer cells exhibit increased ability to form distant metastases in vivo.

Conclusions:

  • GRP78 plays significant roles in regulating pluripotency and oncogenesis.
  • sGRP78 serves as a marker for a stem-like population in breast cancer.
  • This sGRP78-positive population possesses enhanced metastatic potential, offering a potential therapeutic target.