Functional significance of transgelin‐2 in uterine cervical squamous cell carcinoma

Yakabe, Kazuyuki; Murakami, Akihiro; Kajimura, Takuya; Nishimoto, Yuki; Sueoka, Kotaro; Sato, Shun; Nawata, Sumihiko; Sugino, Norihiro

doi:10.1111/jog.12935

Cited by 28 publications

(27 citation statements)

References 16 publications

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“…Transgelin 2 is reported to be implicated in tumorigenesis, boosting tumor progression and promoting metastases (11). Additionally, abnormal expression of transgelin 2 was discovered in lung, gastric and colorectal cancer (12–14).…”

Section: Introductionmentioning

confidence: 99%

SB-T-121205, a next-generation taxane, enhances apoptosis and inhibits migration/invasion in MCF-7/PTX cells

Zheng

Wang

Yang

et al. 2017

International Journal of Oncology

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Breast cancer is the leading cause of cancer death among women. Paclitaxel, a mitotic inhibitor, is highly effective in the treatment of breast cancer. However, development of resistance to paclitaxel limits its clinical use. Identifying new compounds and new strategies that are effective against breast cancer, in particular drug-resistant cancer, is of great importance. The aim of the present study was to explore the potential of a next-generation taxoid, SB-T-121205, in modulating the proliferation, migration and invasion of paclitaxel-resistant human breast cancer cells (MCF-7/PTX) and further evaluate the underlying molecular mechanisms. The results of MTT assay showed that SB-T-121205 has much higher potency to human breast cancer cells (MCF-7/S, MCF-7/PTX and MDA-MB-453 cells) than paclitaxel, while that the non-tumorigenic human bronchial epithelial cells (BEAS-2B) were slightly less sensitive to SB-T-121205 than paclitaxel. Flow cytometry and western blot methods revealed that SB-T-121205 induced cell cycle arrest at the G2/M phase and apoptosis in MCF-7/PTX cells through accelerating mitochondrial apoptotic pathway, resulting in reduction of Bcl-2/Bax ratio, as well as elevation of caspase-3, caspase-9, and poly(ADP-ribose) polymerase (PARP) levels. Moreover, SB-T-121205 changed epithelial-mesenchymal transition (EMT) property, and suppressed migration and invasion abilities of MCF-7/PTX cells. Additionally, SB-T-121205 exerted antitumor activity by inhibiting the transgelin 2 and PI3K/Akt pathway. These findings indicate that SB-T-121205 is a potent antitumor agent that promotes apoptosis and also recedes migration/invasion abilities of MCF-7/PTX cells by restraining the activity of transgelin 2 and PI3K/Akt, as well as mitochondrial apoptotic pathway. Such results suggest a potential clinical value of SB-T-121205 in breast cancer treatment.

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Section: Introductionmentioning

confidence: 99%

SB-T-121205, a next-generation taxane, enhances apoptosis and inhibits migration/invasion in MCF-7/PTX cells

Zheng

Wang

Yang

et al. 2017

International Journal of Oncology

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“…22,[57][58][59] Suppression of TAGLN2 inhibits proliferation and migration of cervical carcinoma cells. 60 Intriguingly, we found this protein to be located exclusively in the vascular endothelium by IHC and therefore could not verify the data of proteomics and RT-PCR analysis. DDX5/p68 is an ATP-dependent RNA helicase and co-activator of transcription factors and thereby plays a role in RNA metabolism.…”

Section: Discussionmentioning

confidence: 63%

Proteomic identification of potential biomarkers for cervical squamous cell carcinoma and human papillomavirus infection

Song

Tulake

et al. 2017

Tumour Biol.

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It is known that high-risk human papillomavirus infection is the main etiological factor in cervical carcinogenesis. However, human papillomavirus screening is not sufficient for early diagnosis. In this study, we aimed to identify potential biomarkers common to cervical carcinoma and human papillomavirus infection by proteomics for human papillomavirus-based early diagnosis and prognosis. To this end, we collected 76 cases of fresh cervical tissues and 116 cases of paraffin-embedded tissue slices, diagnosed as cervical squamous cell carcinoma, cervical intraepithelial neoplasia II-III, or normal cervix from ethnic Uighur and Han women. Human papillomavirus infection by eight oncogenic human papillomavirus types was detected in tissue DNA samples using a quantitative polymerase chain reaction. The protein profile of cervical specimens from human papillomavirus 16-positive squamous cell carcinoma and human papillomavirus-negative normal controls was analyzed by proteomics and bioinformatics. The expression of candidate proteins was further determined by quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry. We identified 67 proteins that were differentially expressed in human papillomavirus 16-positive squamous cell carcinoma compared to normal cervix. The quantitative reverse transcriptase-polymerase chain reaction analysis verified the upregulation of ASAH1, PCBP2, DDX5, MCM5, TAGLN2, hnRNPA1, ENO1, TYPH, CYC, and MCM4 in squamous cell carcinoma compared to normal cervix (p < 0.05). In addition, the transcription of PCBP2, MCM5, hnRNPA1, TYPH, and CYC was also significantly increased in cervical intraepithelial neoplasia II-III compared to normal cervix. Immunohistochemistry staining further confirmed the overexpression of PCBP2, hnRNPA1, ASAH1, and DDX5 in squamous cell carcinoma and cervical intraepithelial neoplasia II-III compared to normal controls (p < 0.05). Our data suggest that the expression of ASAH1, PCBP2, DDX5, and hnRNPA1, and possibly MCM4, MCM5, CYC, ENO1, and TYPH, is upregulated during cervical carcinogenesis and potentially associated with human papillomavirus infection. Further validation studies of the profile will contribute to establishing auxiliary diagnostic markers for human papillomavirus-based cancer prognosis. KeywordsCervical carcinoma, isobaric tags for relative and absolute quantitation, proteomics, human papillomavirus infection, cervical specimen Date

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“…MYH9 and PLS3 have never been implicated in gastric cancer. TAGLN2 promote tumor cell migration and invasion15 and is highly expressed in human pancreatic cancer16 and gastric cancer17.…”

Section: Resultsmentioning

confidence: 99%

Identification of specific biomarkers for gastric adenocarcinoma by ITRAQ proteomic approach

Wang

Zhi

Liu

et al. 2016

Sci Rep

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The aim of this study was to identify biomarkers for gastric cancer (GC) by iTRAQ. Using proteins extracted from a panel of 4 pairs of gastric adenocarcinoma samples (stage III-IV, Her-2 negative), we identified 10 up regulated and 9 down regulated proteins in all four pairs of GC samples compared to adjacent normal gastric tissue. The up regulated proteins are mainly involved in cell motility, while the down regulated proteins are mitochondrial enzymes involved in energy metabolism. The expression of three up regulated proteins (ANXA1, NNMT, fibulin-5) and one of the down regulated proteins (UQCRC1) was validated by Western Blot in 97 GC samples. ANXA1 was up regulated in 61.36% of stage I/II GC samples compared to matched adjacent normal gastric tissue, and its expression increased further in stage III/IV samples. Knockdown of ANXA1 by siRNA significantly inhibited GC cell migration and invasion, whereas over expression of ANXA1 promoted migration and invasion. We found decreased expression of UQCRC1 in all stages of GC samples. Our data suggest that increased cell motility and decreased mitochondrial energy metabolism are important hallmarks during the development of GC.

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Functional significance of transgelin‐2 in uterine cervical squamous cell carcinoma

Abstract: TAGLN2 plays functional roles in the progression of cervical SCC. Suppression of TAGLN2 may be a new strategy for the treatment of cervical SCC.

Cited by 28 publications

References 16 publications

SB-T-121205, a next-generation taxane, enhances apoptosis and inhibits migration/invasion in MCF-7/PTX cells

SB-T-121205, a next-generation taxane, enhances apoptosis and inhibits migration/invasion in MCF-7/PTX cells

Proteomic identification of potential biomarkers for cervical squamous cell carcinoma and human papillomavirus infection

Identification of specific biomarkers for gastric adenocarcinoma by ITRAQ proteomic approach

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