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TAGLN mediated stiffness-regulated ovarian cancer progression via RhoA/ROCK pathway
- Source :
- Journal of Experimental & Clinical Cancer Research, Vol 40, Iss 1, Pp 1-14 (2021), Journal of Experimental & Clinical Cancer Research : CR
- Publication Year :
- 2021
- Publisher :
- BMC, 2021.
-
Abstract
- Background: Ovarian cancer (OC) progression is an unmet medical challenge. Since omental metastases were palpated harder than their primary counterparts during cytoreductive surgery of patients with epithelial ovarian cancer, we were inspired to investigate OC progression from the perspective of biomechanics. Methods: Atomic Force Microscope (AFM) was used to measure the young’s moduli of tissues. The collagen-coated polyacrylamide hydrogel (PA gel) system was prepared to mimic the soft and stiff substrates in vitro. The effect of TAGLN were evaluated both in vitro and in vivo using transwell, immunofluorescence, western blot analysis and immunohistochemistry. Findings: We quantitatively confirmed that omental metastases were stiffer and more abundant in desmoplasia compared with paired primary tumors, and further demonstrated that matrix stiffness could notably regulate OC progression. Remarkably, TAGLN, encoding an actin cross-linking/gelling protein, was identified as a potent mechanosensitive gene that could form a regulation loop with Src activation reacting to environmental stiffness, thus mediating stiffness-regulated OC progression through regulating RhoA/ROCK pathway. Interpretation: These data demonstrate that targeting extra-cellular matrix stiffness could probably hamper OC progression, and of note, targeting TAGLN might provide promising clinical therapeutic value for OC therapy. Funding: This work was supported by the “973” Program of China (No. 2015CB553903 to Ding Ma and Junbo Hu), Technical Innovation Special Project of Hubei Province (2018ACA138), the Fundamental Research Funds for the Central Universities (2019kfyXMBZ024), National Science and Technology Major Sub- Project (2018ZX10301402-002), and the National Science Foundation of China (81902661, 81772787, 82072889). Declaration of Interest: None to declare. Ethical Approval: Human ovarian cancer tissues were all obtained from patients undergoing surgery at the Department of Obstetrics and Gynecology, Tongji Hospital, Huazhong University of Science and Technology after obtaining written informed consent of the patients and the authorization of the Ethics Committee of Tongji Hospital (TJ-iRB20181103). Fresh tissues were prepared for the Atomic Force Microscope (AFM) measurement, frozen or formalin fixed.
- Subjects :
- Cancer Research
RHOA
Fluorescent Antibody Technique
Gene Expression
Muscle Proteins
Mice
Tumor Microenvironment
Medicine
Neoplasm Metastasis
RC254-282
Ovarian Neoplasms
rho-Associated Kinases
medicine.diagnostic_test
biology
Progression
Chemistry
Microfilament Proteins
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Prognosis
Extracellular Matrix
src-Family Kinases
Oncology
Disease Progression
Immunohistochemistry
Female
medicine.symptom
Proto-oncogene tyrosine-protein kinase Src
Signal Transduction
TAGLN
Immunofluorescence
Models, Biological
Tissue mechanics
Western blot
In vivo
Ovarian cancer
Cell Line, Tumor
Animals
Humans
business.industry
Research
Gene Expression Profiling
medicine.disease
Desmoplasia
Disease Models, Animal
Cancer research
biology.protein
RhoA/ROCK
business
rhoA GTP-Binding Protein
Subjects
Details
- Language :
- English
- ISSN :
- 17569966 and 10301402
- Volume :
- 40
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Journal of Experimental & Clinical Cancer Research
- Accession number :
- edsair.doi.dedup.....8d619a2abe70fd9c62913cf64b84f88a