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Cellular apoptosis susceptibility (CSE1L/CAS) protein in cancer metastasis and chemotherapeutic drug-induced apoptosis.

Tai CJ, Hsu CH, Shen SC, Lee WR, Jiang MC - J. Exp. Clin. Cancer Res. (2010)

Bottom Line: CSE1L was originally regarded as a proliferation-associated protein and was thought to regulate the proliferation of cancer cells in cancer progression.However, the results of experimental studies showed that enhanced CSE1L expression is unable to increase proliferation of cancer cells and CSE1L regulates invasion and metastasis but not proliferation of cancer cells.Recent studies revealed that CSE1L is a secretory protein, and there is a higher prevalence of secretory CSE1L in the sera of patients with metastatic cancer.

View Article: PubMed Central - HTML - PubMed

Affiliation: Section of Hematology-Oncology, Department of Medicine, Taipei Medical University and Hospital, Taipei, Taiwan.

ABSTRACT
The cellular apoptosis susceptibility (CSE1L/CAS) protein is highly expressed in cancer, and its expression is positively correlated with high cancer stage, high cancer grade, and worse outcomes of patients. CSE1L (or CAS) regulates chemotherapeutic drug-induced cancer cell apoptosis and may play important roles in mediating the cytotoxicities of chemotherapeutic drugs against cancer cells in cancer chemotherapy. CSE1L was originally regarded as a proliferation-associated protein and was thought to regulate the proliferation of cancer cells in cancer progression. However, the results of experimental studies showed that enhanced CSE1L expression is unable to increase proliferation of cancer cells and CSE1L regulates invasion and metastasis but not proliferation of cancer cells. Recent studies revealed that CSE1L is a secretory protein, and there is a higher prevalence of secretory CSE1L in the sera of patients with metastatic cancer. Therefore, CSE1L may be a useful serological marker for screening, diagnosis and prognosis, assessment of therapeutic responses, and monitoring for recurrence of cancer. In this paper, we review the expression of CSE1L in cancer and discuss why CSE1L regulates the invasion and metastasis rather than the proliferation of cancer.

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CSE1L staining in vesicles surrounding the outside of cell membrane. The distribution of CSE1L in MCF-7 cells was analyzed by immunohistochemistry with anti-CSE1L antibody. Note the vesicle-like staining of CSE1L in cell protrusions and positive staining of CSE1L in vesicles surrounding the outside of the cell membrane. The scale bar = 30 μm. The photo is derived from a figure in reference 63 [63].
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Figure 1: CSE1L staining in vesicles surrounding the outside of cell membrane. The distribution of CSE1L in MCF-7 cells was analyzed by immunohistochemistry with anti-CSE1L antibody. Note the vesicle-like staining of CSE1L in cell protrusions and positive staining of CSE1L in vesicles surrounding the outside of the cell membrane. The scale bar = 30 μm. The photo is derived from a figure in reference 63 [63].

Mentions: CSE1L is highly expressed in cancer, and its expression level is well correlated with advanced cancer stage and worse patient outcomes. Therefore, CSE1L may play an important role in cancer progression. CSE1L is a microtubule-associated protein [4]. Our recent study showed that the association of CSE1L with microtubules is related with protrusion extension and migration of MCF-7 breast cancer cells [80]. In the immunofluorescence study, CSE1L was colocalized with MMP-2 in vesicles surrounding the outside of the MCF-7 cell membranes [Fig 1; also see [63]]. Since MMP-2 is a secretory protein, these results suggest that CSE1L may be secreted together with MMP-2. In immunohistochemistry, positive CSE1L staining was observed in the gland lumen of different cancers including breast cancer and colorectal cancer [63]. The tumor microenvironment, or stroma, consists of ECM and plays an important role in regulating cancer metastasis [81,82]. Glands, the major epithelial components of tubular organs, mediate the passage and control of homeostasis by modifying secretion. Glands in cancer tissues also provide the metastatic cancer cells with a route for invasion to adjacent tissues or other organs [83]. Moreover, substances that are secreted from a gland lumen can ultimately reach blood vessels [84]. CSE1L staining in the gland lumen of metastatic cancer tissues indicate that CSE1L may be secreted by cancer tissues and CSE1L may be a secretory protein.


Cellular apoptosis susceptibility (CSE1L/CAS) protein in cancer metastasis and chemotherapeutic drug-induced apoptosis.

Tai CJ, Hsu CH, Shen SC, Lee WR, Jiang MC - J. Exp. Clin. Cancer Res. (2010)

CSE1L staining in vesicles surrounding the outside of cell membrane. The distribution of CSE1L in MCF-7 cells was analyzed by immunohistochemistry with anti-CSE1L antibody. Note the vesicle-like staining of CSE1L in cell protrusions and positive staining of CSE1L in vesicles surrounding the outside of the cell membrane. The scale bar = 30 μm. The photo is derived from a figure in reference 63 [63].
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2925819&req=5

Figure 1: CSE1L staining in vesicles surrounding the outside of cell membrane. The distribution of CSE1L in MCF-7 cells was analyzed by immunohistochemistry with anti-CSE1L antibody. Note the vesicle-like staining of CSE1L in cell protrusions and positive staining of CSE1L in vesicles surrounding the outside of the cell membrane. The scale bar = 30 μm. The photo is derived from a figure in reference 63 [63].
Mentions: CSE1L is highly expressed in cancer, and its expression level is well correlated with advanced cancer stage and worse patient outcomes. Therefore, CSE1L may play an important role in cancer progression. CSE1L is a microtubule-associated protein [4]. Our recent study showed that the association of CSE1L with microtubules is related with protrusion extension and migration of MCF-7 breast cancer cells [80]. In the immunofluorescence study, CSE1L was colocalized with MMP-2 in vesicles surrounding the outside of the MCF-7 cell membranes [Fig 1; also see [63]]. Since MMP-2 is a secretory protein, these results suggest that CSE1L may be secreted together with MMP-2. In immunohistochemistry, positive CSE1L staining was observed in the gland lumen of different cancers including breast cancer and colorectal cancer [63]. The tumor microenvironment, or stroma, consists of ECM and plays an important role in regulating cancer metastasis [81,82]. Glands, the major epithelial components of tubular organs, mediate the passage and control of homeostasis by modifying secretion. Glands in cancer tissues also provide the metastatic cancer cells with a route for invasion to adjacent tissues or other organs [83]. Moreover, substances that are secreted from a gland lumen can ultimately reach blood vessels [84]. CSE1L staining in the gland lumen of metastatic cancer tissues indicate that CSE1L may be secreted by cancer tissues and CSE1L may be a secretory protein.

Bottom Line: CSE1L was originally regarded as a proliferation-associated protein and was thought to regulate the proliferation of cancer cells in cancer progression.However, the results of experimental studies showed that enhanced CSE1L expression is unable to increase proliferation of cancer cells and CSE1L regulates invasion and metastasis but not proliferation of cancer cells.Recent studies revealed that CSE1L is a secretory protein, and there is a higher prevalence of secretory CSE1L in the sera of patients with metastatic cancer.

View Article: PubMed Central - HTML - PubMed

Affiliation: Section of Hematology-Oncology, Department of Medicine, Taipei Medical University and Hospital, Taipei, Taiwan.

ABSTRACT
The cellular apoptosis susceptibility (CSE1L/CAS) protein is highly expressed in cancer, and its expression is positively correlated with high cancer stage, high cancer grade, and worse outcomes of patients. CSE1L (or CAS) regulates chemotherapeutic drug-induced cancer cell apoptosis and may play important roles in mediating the cytotoxicities of chemotherapeutic drugs against cancer cells in cancer chemotherapy. CSE1L was originally regarded as a proliferation-associated protein and was thought to regulate the proliferation of cancer cells in cancer progression. However, the results of experimental studies showed that enhanced CSE1L expression is unable to increase proliferation of cancer cells and CSE1L regulates invasion and metastasis but not proliferation of cancer cells. Recent studies revealed that CSE1L is a secretory protein, and there is a higher prevalence of secretory CSE1L in the sera of patients with metastatic cancer. Therefore, CSE1L may be a useful serological marker for screening, diagnosis and prognosis, assessment of therapeutic responses, and monitoring for recurrence of cancer. In this paper, we review the expression of CSE1L in cancer and discuss why CSE1L regulates the invasion and metastasis rather than the proliferation of cancer.

Show MeSH
Related in: MedlinePlus