Related Experiment Videos
HSPA4 Knockdown Retarded Progression and Development of Colorectal Cancer
Mingliang Zhang1, Weigang Dai1, Zhanyu Li1
1Department of Colorectal Surgery, Gastrointestinal Surgery Center, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, Guangdong Province, People's Republic of China.
Purpose:
Colorectal cancer (CRC) is a common malignancy associated with high morbidity and mortality. Heat shock 70 kDa protein 4 (HSPA4) has been shown to exert regulatory roles during tumor progression in different cancer types. Here, we investigated the expression and cellular functions of HSPA4 in CRC.
Materials And Methods:
Expression of HSPA4 in CRC tissues and paracancerous tissues was analyzed by RT-qPCR and immunohistochemistry IHC staining. The functional roles of HSPA4 were explored using shRNA-mediated knockdown in HCT116 and RKO CRC cell lines, both in vitro and in tumor xenograft studies.
Results:
HSPA4 expression was significantly increased at the RNA and protein levels in CRC tissues compared with noncancerous tissues. Moreover, HSPA4 expression was positively associated with tumor stage and its high expression of HSPA4 indicated poor patient prognosis. In vitro studies established that HSPA4 knockdown inhibited proliferation and migration, causing arrest in the G2-phase of the cell cycle along with increased levels of apoptosis. This phenotype was recapitulated in vivo where HSPA4 knockdown suppressed xenograft growth. Mechanistic investigations showed silencing of HSPA4 reduced activation of the PI3K, Akt signaling axis while also downregulating the cell cycle progression markers, CCND1 and CDK6. Similarly, there was altered expression of apoptosis-related proteins consistent with the increase in apoptosis.
Conclusion:
Our findings demonstrate clinical significance for HSPA4 in CRC, further showing that HSPA4 contributes to CRC tumorigenesis through effects on proliferation, migration and survival. Thus, HSPA4 represents a novel prognostic indicator as well as a promising therapeutic target in CRC.
Insights
Heat shock protein HSPA4 (HSPA4) is elevated in colorectal cancer (CRC) and promotes tumor growth by affecting cell proliferation, migration, and survival. Targeting HSPA4 may offer a new therapeutic strategy for CRC patients.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Colorectal cancer (CRC) presents a significant global health challenge due to high morbidity and mortality.
- Heat shock 70 kDa protein 4 (HSPA4) is implicated in the progression of various cancer types.
- Understanding HSPA4's role in CRC is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the expression levels of HSPA4 in colorectal cancer tissues.
- To elucidate the functional significance of HSPA4 in CRC cell proliferation, migration, and survival.
- To evaluate HSPA4 as a potential prognostic biomarker and therapeutic target in CRC.
Main Methods:
- Quantitative real-time PCR (RT-qPCR) and immunohistochemistry (IHC) were used to analyze HSPA4 expression in CRC and adjacent tissues.
- In vitro studies involved shRNA-mediated knockdown of HSPA4 in HCT116 and RKO CRC cell lines.
- In vivo experiments utilized tumor xenograft models to assess the effects of HSPA4 knockdown on tumor growth.
Main Results:
- HSPA4 expression was significantly upregulated in CRC tissues at both RNA and protein levels compared to non-cancerous tissues.
- HSPA4 overexpression correlated with advanced tumor stage and predicted poor patient prognosis.
- Knockdown of HSPA4 inhibited CRC cell proliferation and migration, induced G2-phase cell cycle arrest, and promoted apoptosis, effects mirrored in vivo.
- Mechanistically, HSPA4 silencing reduced PI3K/Akt signaling pathway activation and altered the expression of cell cycle regulators (CCND1, CDK6) and apoptosis-related proteins.
Conclusions:
- HSPA4 plays a critical role in colorectal cancer tumorigenesis, influencing proliferation, migration, and survival.
- HSPA4 is a clinically significant protein in CRC, serving as a novel prognostic indicator.
- HSPA4 emerges as a promising therapeutic target for colorectal cancer treatment.