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Updated: Aug 27, 2025
A Quantitative Cell Migration Assay for Murine Enteric Neural Progenitors
Published on: September 18, 2013
DLC1 inhibits colon adenocarcinoma cell migration by promoting secretion of the neurotrophic factor MANF
Yi-Min Chu1, Ying Xu1, Xiu-Qun Zou2
1Digestive Endoscopy Center, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Abstract:
DLC1 (deleted in liver cancer-1) is downregulated or deleted in colorectal cancer (CRC) tissues and functions as a potent tumor suppressor, but the underlying molecular mechanism remains elusive. We found that the conditioned medium (CM) collected from DLC1-overexpressed SW1116 cells inhibited the migration of colon adenocarcinoma cells HCT116 and SW1116, but had no effect on proliferation, which suggested DLC1-mediated secretory components containing a specific inhibitor for colon adenocarcinoma cell migration. Analysis by mass spectrometry identified mesencephalic astrocyte-derived neurotrophic factor (MANF) as a candidate. More importantly, exogenous MANF significantly inhibited the migration of colon adenocarcinoma cells HCT116 and SW1116, but did not affect proliferation. Mechanistically, DLC1 reduced the retention of MANF in ER by competing the interaction between MANF and GRP78. Taken together, these data provided new insights into the suppressive effects of DLC1 on CRC, and revealed the potential of MANF in the treatment of CRC.
Insights
Deleted in liver cancer-1 (DLC1) suppresses colorectal cancer (CRC) by inhibiting cell migration. DLC1 promotes the secretion of mesencephalic astrocyte-derived neurotrophic factor (MANF), a novel inhibitor of colon cancer cell migration.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Deleted in liver cancer-1 (DLC1) is a tumor suppressor frequently lost in colorectal cancer (CRC).
- The molecular mechanisms underlying DLC1's tumor-suppressive functions in CRC remain largely unknown.
- Understanding DLC1's role is crucial for developing novel CRC therapies.
Purpose of the Study:
- To elucidate the molecular mechanism by which DLC1 suppresses colorectal cancer.
- To identify DLC1-mediated secretory factors that inhibit colon adenocarcinoma cell migration.
- To investigate the therapeutic potential of identified factors in CRC.
Main Methods:
- Mass spectrometry-based proteomic analysis of conditioned medium from DLC1-overexpressing cells.
- In vitro cell migration and proliferation assays using colon adenocarcinoma cell lines (HCT116, SW1116).
- Co-immunoprecipitation and Western blot analysis to investigate protein-protein interactions.
Main Results:
- DLC1 overexpression in SW1116 cells inhibited colon adenocarcinoma cell migration but not proliferation.
- Mass spectrometry identified mesencephalic astrocyte-derived neurotrophic factor (MANF) as a candidate secreted factor.
- Exogenous MANF inhibited colon adenocarcinoma cell migration independently of proliferation.
- DLC1 competitively inhibited the interaction between MANF and GRP78, reducing MANF retention in the ER.
Conclusions:
- DLC1 exerts tumor-suppressive effects in CRC by inhibiting cell migration through the secretion of MANF.
- MANF acts as a novel inhibitor of colon adenocarcinoma cell migration.
- The DLC1-MANF axis represents a potential therapeutic target for colorectal cancer treatment.
