Tight Junction Protein 1 Suppresses Kidney Renal Clear Cell Carcinoma Cells Proliferation by Inducing Autophagy
Miao Li1,2, Di-Sheng Zhou1, Xin-Rong Shao1
1Shenzhen Key Laboratory for Systems Medicine in Inflammatory Diseases, School of Medicine, Shenzhen Campus of Sun Yat-Sen University, The Seventh Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Shenzhen, China.
Abstract:
TJP1, an adaptor protein of the adhesive barrier, has been found to exhibit distinct oncogenic or tumor suppressor functions in a cell-type dependent manner. However, the role of TJP1 in kidney renal clear cell carcinoma (KIRC) remains to be explored. The results showed a marked down-regulation of TJP1 in KIRC tissues compared to normal tissues. Low expression of TJP1 was significantly associated with high grade and poor prognosis in KIRC. Autophagosome aggregation and LC3 II conversion demonstrated that TJP1 may induce autophagy signaling in 786-O and OS-RC-2 cells. Knockdown of TJP1 led to a decrease in the expression of autophagy-related genes, such as BECN1, ATG3, and ATG7. Consistently, TJP1 expression showed a significant positive correlation with these autophagy-related genes in KIRC patients. Furthermore, the overall survival analysis of KIRC patients based on the expression of autophagy-related genes revealed that most of these genes were associated with a good prognosis. TJP1 overexpression significantly suppressed cell proliferation and tumor growth in 786-O cells, whereas the addition of an autophagy inhibitor diminished its inhibitory function. Taken together, these results suggest that TJP1 serves as a favorable prognostic marker and induces autophagy to suppress cell proliferation and tumor growth in KIRC.
Insights
Tight junction protein 1 (TJP1) is downregulated in kidney renal clear cell carcinoma (KIRC). TJP1 promotes autophagy, suppressing tumor growth and indicating a favorable prognosis for KIRC patients.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Tight junction protein 1 (TJP1) has varied roles in cancer, but its function in kidney renal clear cell carcinoma (KIRC) is unknown.
- TJP1 is an adaptor protein crucial for the adhesive barrier in cells.
Purpose of the Study:
- To investigate the role of TJP1 in kidney renal clear cell carcinoma (KIRC).
- To determine the prognostic significance of TJP1 in KIRC.
- To elucidate the mechanism by which TJP1 affects KIRC progression, focusing on autophagy.
Main Methods:
- Quantitative analysis of TJP1 expression in KIRC tissues versus normal tissues.
- Correlation analysis between TJP1 expression, clinicopathological features (grade), and patient prognosis.
- In vitro studies using KIRC cell lines (786-O, OS-RC-2) to assess TJP1's effect on autophagy signaling (autophagosome aggregation, LC3 II conversion).
- Gene expression analysis of autophagy-related genes (BECN1, ATG3, ATG7) following TJP1 knockdown.
- Functional assays evaluating the impact of TJP1 overexpression on cell proliferation and tumor growth, with and without autophagy inhibitors.
Main Results:
- TJP1 expression was significantly downregulated in KIRC tissues compared to normal tissues.
- Low TJP1 expression correlated with higher tumor grade and poorer prognosis in KIRC patients.
- TJP1 induced autophagy signaling and was positively correlated with key autophagy-related genes (BECN1, ATG3, ATG7), which were associated with a good prognosis.
- TJP1 overexpression suppressed KIRC cell proliferation and tumor growth, an effect attenuated by autophagy inhibition.
Conclusions:
- TJP1 acts as a tumor suppressor in KIRC by inducing autophagy.
- TJP1 represents a favorable prognostic biomarker for kidney renal clear cell carcinoma.
- Targeting TJP1-mediated autophagy may offer a therapeutic strategy for KIRC.
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