Title:MFAP5 Strengthened the Stem Cell Features of Non-small Cell Lung Cancer Cells by Regulating the FBW/Sox9 Axis
Volume: 25
Author(s): Chun Du*, Zijuan Qi and Wei Zhang
Affiliation:
- Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang Province, 150081, China
Keywords:
Non-small cell lung cancer, MFAP5, Cancer stem cells, Sox9.
Abstract: Introduction: Non-small cell lung cancer (NSCLC) is a type of malignant tumor with
high morbidity as well as mortality. The process of lung cancer may be driven by cancer stem
cells. It was known that MFAP5 enhanced the occurrence of diverse types of cancer. Also,
MFAP5 has the potential to induce the degradation of FBW7 which is a tumor suppressor. Lower
levels of FBW7 enhance the stability of Sox9, which is the cancer stem cell-related protein.
However, whether the MFAP5 can modulate the stem cell features of NSCLC cells by modulating
the FBW7/Sox9 axis is unclear. Therefore, this study aimed to explore the role of
MFAP5/FBW7/Sox9 axis on the stem cell features of NSCLC cells and develop a new treatment
of this carcinoma.
Material and Methods: In this study, we explored the effects of MFAP5 on the stem cell features
of NSCLC cells for the first time. We established MFAP5 overexpression and knockdown
NSCLC cells. Clone formation assays and cell sphere culture assays were conducted for the exploration
of the growth and stem cell features of these cells. Western blotting was applied for the
detection of Sox9 and FBW7 expression in these cells. CHX was applied for the treatment of
these cells for the detection of degradation of Sox9. Finally, we overexpressed the Sox9 in
MFAP5 knockdown NSCLC cells.
Results: MFAP5 promoted the growth and stem cell features of these cells. Knockdown of
MFAP5 induced higher levels of FBW7 while restricting the expression of Sox9. Knockdown of
MFAP5 aggravated the degradation of Sox9. Overexpression of Sox9 abrogated the efficacy of
MFAP5 inhibition on the growth as well as stem cell features of these cells. The results of this
study clarified the role of MFAP5/FBW7/Sox9 axis on the development of non-small cell lung
cancer cells, providing the potential therapeutic target for the clinical treatment of NSCLC.
Conclusion: MFAP5 maintained the stem cell features of non-small cell lung cancer cells by
modulating FBW7/Sox9 axis.
