Tumor suppressor genes and their underlying interactions in paclitaxel resistance in cancer therapy.

Jia-Hui Xu,Gan Shen,Guo-Dong Shen,Shi-Lian Hu

doi:10.1186/s12935-016-0290-9

Jia-Hui Xu, Gan Shen + Show 2 more

Open Access

https://doi.org/10.1186/s12935-016-0290-9

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Abstract

ObjectivesPaclitaxel (PTX) is frequently used in the clinical treatment of solid tumors. But the PTX-resistance is a great obstacle in cancer treatment. Exploration of the mechanisms of drug resistance suggests that tumor suppressor genes (TSGs) play a key role in the response of chemotherapeutic drugs. TSGs, a set of genes that are often inactivated in cancers, can regulate various biological processes. In this study, an overview of the contribution of TSGs to PTX resistance and their underlying relationship in cancers are reported by using GeneMANIA, a web-based tool for gene/protein function prediction.MethodsUsing PubMed online database and Google web site, the terms “paclitaxel resistance” or “taxol resistance” or “drug resistance” or “chemotherapy resistance”, and “cancer” or “carcinoma”, and “tumor suppressor genes” or “TSGs” or “negative regulated protein” or “antioncogenes” were searched and analyzed. GeneMANIA data base was used to predict gene/protein interactions and functions.ResultsWe identified 22 TSGs involved in PTX resistance, including BRCA1, TP53, PTEN, APC, CDKN1A, CDKN2A, HIN-1, RASSF1, YAP, ING4, PLK2, FBW7, BLU, LZTS1, REST, FADD, PDCD4, TGFBI, ING1, Bax, PinX1 and hEx. The TSGs were found to have direct and indirect relationships with each other, and thus they could contribute to PTX resistance as a group. The varied expression status and regulation function of the TSGs on cell cycle in different cancers might play an important role in PTX resistance.ConclusionA further understanding of the roles of tumor suppressor genes in drug resistance is an important step to overcome chemotherapy tolerance. Tumor suppressor gene therapy targets the altered genes and signaling pathways and can be a new strategy to reverse chemotherapy resistance.

Highlights

Chemotherapy is the main cancer treatment modality, among which paclitaxel (PTX) is a type of cytotoxic agent and widely used in the first line treatment of lung, ovarian, breast, renal cancers and Kaposi’s sarcoma [1,2,3,4,5]
We identified 22 tumor suppressor genes (TSGs) involved in PTX resistance, including breast cancer 1 (BRCA1), tumor protein p53 (TP53), phosphatase and tension homolog (PTEN), adenomatous polyposis coli (APC), cyclin-dependent kinase inhibitor 1A (CDKN1A), cyclin-dependent kinase inhibitor 2A (CDKN2A), high in normal-1 (HIN-1), ras association domain-containing protein 1 (RASSF1), yes-associated protein 1 (YAP), inhibitor of growth 4 (ING4), polo-like kinase 2 (PLK2), f-box and WD repeat domain containing 7 (FBW7), zinc finger MYND domain-containing protein 10 (BLU), leucine zipper tumor suppressor 1 (LZTS1), re-1 silencing transcription factor (REST), fas-associated death domain protein (FADD), programmed cell death 4 (PDCD4), transforming growth factor-β-induced (TGFBI), inhibitor of growth 1 (ING1), bcl-2-associated X protein (Bax), the telomere/telomerase binding factor (PinX1) and human homolog of drosophila expanded (hEx)
It is well known that TSGs play an important role in cell cycle, angiogenesis and signal transduction, and currently TSGs are considered to participate in the formation of chemo-resistance

Summary

Methods

Using PubMed online database and Google web site, the terms “paclitaxel resistance” or “taxol resistance” or “drug resistance” or “chemotherapy resistance”, and “cancer” or “carcinoma”, and “tumor suppressor genes” or “TSGs” or “negative regulated protein” or “antioncogenes” were searched and analyzed. GeneMANIA data base was used to predict gene/protein interactions and functions

Results

Conclusion

Background