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SPINK4 promotes colorectal cancer cell proliferation and inhibits ferroptosis
Bang-Li Hu1, Yi-Xin Yin2, Ke-Zhi Li2
1Department of Research, Guangxi Medical University Cancer Hospital, No. 71 Hedi Road, Nanning, 530021, Guangxi, PR China. hubangli@gxmu.edu.cn.
Background:
Little is known about the role of serine peptidase inhibitor Kazal type 4 (SPINK4) in colorectal cancer (CRC) and ferroptosis. Therefore, this study aimed to determine the effect of SPINK4 on CRC pathogenesis and ferroptosis.
Methods:
SPINK4 expression was analyzed in public datasets and examined using immunohistochemistry. The biological function of SPINK4 in CRC cell lines and its effect on ferroptosis were tested. An immunofluorescence assay was performed to determine the location of SPINK4 in cells, and mouse models were established to determine the effects of SPINK4 in vivo.
Results:
CRC datasets and clinical samples analysis revealed that SPINK4 mRNA and protein levels were significantly reduced in CRC tissues compared to control tissues (P < 0.05). Two CRC cell lines (HCT116 and LoVo) were selected, and the in vitro and in vivo experiments showed that overexpression of SPINK4 greatly promotes the proliferation and metastasis of CRC cells and tumor growth (P < 0.05). The immunofluorescence assay indicated that SPINK4 is mainly located in the nucleoplasm and nucleus of CRC cells. Furthermore, SPINK4 expression was reduced after cell ferroptosis induced by Erastin, and overexpression of SPINK4 greatly inhibited ferroptosis in CRC cells. The results of mouse model further demonstrated that SPINK4 overexpression inhibited CRC cell ferroptosis and facilitated tumor growth.
Conclusions:
SPINK4 was decreased in CRC tissues and promoted cell proliferation and metastasis; overexpression of SPINK4 inhibited CRC cell ferroptosis.
Insights
Serine peptidase inhibitor Kazal type 4 (SPINK4) is reduced in colorectal cancer (CRC) and promotes tumor growth. Overexpression of SPINK4 inhibits CRC cell ferroptosis, a key process in cancer progression.
Area of Science:
- Oncology
- Molecular Biology
- Cell Death Research
Background:
- The role of serine peptidase inhibitor Kazal type 4 (SPINK4) in colorectal cancer (CRC) and ferroptosis remains largely unknown.
- Understanding SPINK4's function is crucial for developing novel therapeutic strategies against CRC.
Purpose of the Study:
- To investigate the effect of SPINK4 on colorectal cancer pathogenesis.
- To determine the impact of SPINK4 on ferroptosis in CRC cells.
Main Methods:
- Analysis of SPINK4 expression in public CRC datasets and clinical samples using immunohistochemistry.
- In vitro studies using CRC cell lines (HCT116, LoVo) to assess SPINK4's biological function and effect on ferroptosis.
- In vivo experiments using mouse models to evaluate SPINK4's role in tumor growth and metastasis.
Main Results:
- SPINK4 mRNA and protein levels were significantly decreased in CRC tissues compared to normal tissues.
- Overexpression of SPINK4 promoted CRC cell proliferation, metastasis, and tumor growth in vitro and in vivo.
- SPINK4 is primarily localized in the nucleoplasm and nucleus of CRC cells.
- SPINK4 expression decreased during Erastin-induced ferroptosis, and SPINK4 overexpression inhibited ferroptosis in CRC cells.
Conclusions:
- SPINK4 is downregulated in colorectal cancer tissues.
- SPINK4 overexpression enhances CRC cell proliferation and metastasis.
- SPINK4 plays an inhibitory role in colorectal cancer cell ferroptosis.
