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Suppression of Pro-fibrotic Signaling Potentiates Factor-mediated Reprogramming of Mouse Embryonic Fibroblasts into Induced Cardiomyocytes
Published on: June 3, 2018
Suppression of src-induced transformed phenotype by expression of tropomyosin-1
G L Prasad1, L Masuelli, M H Raj
1Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
Abstract:
Suppression of high M(r) tropomyosins (TMs) is a common feature of transformed cells. Previous work from this laboratory has demonstrated that the isoform 1 of TM, TM1, acts as an anti-oncogene in ras-transformed murine fibroblasts. In this study, we have investigated whether TM1 is a ras-specific suppressor, or a general suppressor protein of the cellular transformation. V-src transformed fibroblasts, which express decreased TM1, were transduced with a full-length cDNA to overexpress TM1. Both the control and the transduced cells expressed v-src kinase at comparable levels. TM1 expressing (src-T1) cells grew at a lower rate in monolayer, exhibited well spread, flat morphology than the control cells. Enhanced expression of TM1 resulted in improved microfilamental architecture. More significantly, src-T1 cells completely failed to grow under anchorage independent conditions. These data demonstrate that TM1 is as an anti-oncogene of functionally diverse oncogenes, and it is a class II tumor suppressor protein.
Insights
Tropomyosin 1 (TM1) suppresses cellular transformation by diverse oncogenes, not just ras. Overexpressing TM1 in v-src transformed cells reduced growth and anchorage-independent proliferation, confirming its role as a tumor suppressor protein.
Area of Science:
- Cell Biology
- Molecular Oncology
- Cancer Research
Background:
- Suppression of high molecular weight tropomyosins (TMs) is characteristic of transformed cells.
- Tropomyosin 1 (TM1) has been previously identified as an anti-oncogene in ras-transformed murine fibroblasts.
Purpose of the Study:
- To determine if TM1 acts as a ras-specific suppressor or a general suppressor of cellular transformation.
- To investigate the role of TM1 in v-src transformed cells.
Main Methods:
- V-src transformed fibroblasts with decreased TM1 expression were transduced to overexpress TM1.
- Comparative analysis of control and TM1-overexpressing (src-T1) cells regarding growth rate, morphology, and anchorage-independent growth.
Main Results:
- TM1-overexpressing cells exhibited reduced monolayer growth rates and a more spread, flat morphology.
- Enhanced TM1 expression improved microfilament architecture.
- Src-T1 cells demonstrated a complete failure to grow under anchorage-independent conditions.
Conclusions:
- TM1 functions as a general anti-oncogene against functionally diverse oncogenes, including v-src.
- TM1 is classified as a class II tumor suppressor protein.
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