Tumor Suppressor Candidate 2 (TUSC2): Discovery, Functions, and Cancer Therapy
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Published on: June 13, 2019
Austin Arrigo1,2, Angelina T Regua1, Mariana K Najjar1,2
1Department of Neurosurgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Abstract:
Tumor Suppressor Candidate 2 (TUSC2) was first discovered as a potential tumor suppressor gene residing in the frequently deleted 3p21.3 chromosomal region. Since its discovery, TUSC2 has been found to play vital roles in normal immune function, and TUSC2 loss is associated with the development of autoimmune diseases as well as impaired responses within the innate immune system. TUSC2 also plays a vital role in regulating normal cellular mitochondrial calcium movement and homeostasis. Moreover, TUSC2 serves as an important factor in premature aging. In addition to TUSC2's normal cellular functions, TUSC2 has been studied as a tumor suppressor gene that is frequently deleted or lost in a multitude of cancers, including glioma, sarcoma, and cancers of the lung, breast, ovaries, and thyroid. TUSC2 is frequently lost in cancer due to somatic deletion within the 3p21.3 region, transcriptional inactivation via TUSC2 promoter methylation, post-transcriptional regulation via microRNAs, and post-translational regulation via polyubiquitination and proteasomal degradation. Additionally, restoration of TUSC2 expression promotes tumor suppression, eventuating in decreased cell proliferation, stemness, and tumor growth, as well as increased apoptosis. Consequently, TUSC2 gene therapy has been tested in patients with non-small cell lung cancer. This review will focus on the current understanding of TUSC2 functions in both normal and cancerous tissues, mechanisms of TUSC2 loss, TUSC2 cancer therapeutics, open questions, and future directions.
Insights
Tumor Suppressor Candidate 2 (TUSC2) is a crucial gene involved in immune function, aging, and cellular health. Loss of TUSC2 is linked to various cancers, and its restoration shows promise in cancer therapy.
Area of Science:
- Genetics
- Molecular Biology
- Cancer Research
Background:
- Tumor Suppressor Candidate 2 (TUSC2) is a gene located in the 3p21.3 region, known for its tumor-suppressing potential.
- TUSC2 plays critical roles in immune function, mitochondrial calcium regulation, and preventing premature aging.
- Loss or deletion of TUSC2 is observed in numerous cancers, including lung, breast, and ovarian cancers.
Purpose of the Study:
- To review the multifaceted functions of TUSC2 in normal and cancerous tissues.
- To elucidate the mechanisms underlying TUSC2 loss in cancer development.
- To discuss TUSC2-based cancer therapeutics and future research directions.
Main Methods:
- Literature review of studies on TUSC2 function, regulation, and therapeutic applications.
- Analysis of genetic and epigenetic mechanisms leading to TUSC2 inactivation.
- Examination of preclinical and clinical data regarding TUSC2 gene therapy.
Main Results:
- TUSC2 loss is associated with impaired immune responses, autoimmune diseases, and cancer progression.
- Mechanisms of TUSC2 loss include somatic deletion, promoter methylation, and post-transcriptional/translational regulation.
- Restoration of TUSC2 expression inhibits tumor cell proliferation, stemness, and growth, while promoting apoptosis.
Conclusions:
- TUSC2 is a vital tumor suppressor with significant implications in cancer and immune system regulation.
- Understanding TUSC2 loss mechanisms is key to developing effective cancer therapies.
- TUSC2 gene therapy presents a promising therapeutic strategy for various cancers, notably non-small cell lung cancer.
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