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Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
Published on: September 30, 2016
The EF-hand calcium-binding protein tescalcin is a potential oncotarget in colorectal cancer
Yun Hee Kang1, Seung Ro Han, Jong-Tae Kim
1Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea.
Abstract:
Tescalcin (TESC) is an EF-hand calcium binding protein that is differentially expressed in several tissues, however it is not reported that the expression and functional roles of TESC in colorectal cancer. Levels of messenger RNA (mRNA) and protein expression of TESC in colorectal cancer tissues were assessed using RT-PCR, real time PCR, immunohistochemistry, and clinicopathologic analyses. Quantitative analysis of TESC levels in serum specimens was performed using sandwich ELISA. Colorectal cancer cells transfected with TESC small interfering RNA and short hairpin RNA were examined in cell proliferation assays, phospho-MAPK array, and mouse xenograft models. Here we demonstrated that TESC is overexpressed in colorectal cancer (CRC), but was not expressed in normal mucosa and premalignant dysplastic lesions. Furthermore, serum TESC levels were elevated in patients with CRC. Knockdown of TESC inhibited the Akt-dependent NF-κB pathway and decreased cell survival in vitro. Depletion of TESC reduced tumor growth in a CRC xenograft model. Thus, TESC is a potential diagnostic marker and oncotarget in colorectal cancer.
Insights
Tescalcin (TESC) is overexpressed in colorectal cancer (CRC), showing potential as a diagnostic marker. Its depletion inhibits tumor growth and cell survival, highlighting TESC as a therapeutic target for CRC.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Tescalcin (TESC), an EF-hand calcium-binding protein, exhibits differential tissue expression.
- The role and expression of TESC in colorectal cancer (CRC) remain largely uninvestigated.
- Understanding TESC's function in CRC is crucial for identifying new diagnostic and therapeutic strategies.
Purpose of the Study:
- To investigate the expression patterns of TESC in colorectal cancer tissues and serum.
- To elucidate the functional role of TESC in colorectal cancer cell proliferation and tumor growth.
- To evaluate TESC as a potential diagnostic biomarker and therapeutic target for CRC.
Main Methods:
- Quantitative assessment of TESC mRNA and protein levels using RT-PCR, real-time PCR, and immunohistochemistry.
- Serum TESC quantification via sandwich ELISA in colorectal cancer patients.
- Functional studies involving TESC knockdown (siRNA, shRNA) in cell proliferation assays, phospho-MAPK arrays, and mouse xenograft models.
Main Results:
- TESC was significantly overexpressed in colorectal cancer tissues but absent in normal mucosa and premalignant lesions.
- Elevated serum TESC levels were observed in patients diagnosed with colorectal cancer.
- TESC knockdown suppressed colorectal cancer cell survival by inhibiting the Akt-dependent NF-κB pathway and reduced tumor growth in vivo.
Conclusions:
- Tescalcin (TESC) is a promising diagnostic biomarker for colorectal cancer, detectable in serum.
- TESC plays a critical role in colorectal cancer progression, making it a potential therapeutic oncotarget.
- Targeting TESC may offer a novel strategy for colorectal cancer treatment.
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