XRCC1 serves as a potential prognostic indicator for clear cell renal cell carcinoma and inhibits its invasion and metastasis through suppressing MMP-2 and MMP-9

Liu, Qinghua; Wang, You; Yong, Hongmei; Hou, Pingfu; Pan, Jie; Bai, Jing; Zheng, Junnian

doi:10.18632/oncotarget.22680

Cited by 17 publications

(13 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a preclinical MCF10DCIS model, we show that XRCC1 KO dramatically increased invasion associated with upregulation of markers of EMT. Whether XRCC1 is directly or indirectly involved in upregulation of several genes involved in EMT is unknown but the data shown here would concur with previous studies in melanoma (26) and clear cell renal cancer (27) cells where XRCC1 depletion was also shown to promote invasion. A novel observation in this study is that MCF10DCIS_ XRCC1_ KO cells are extremely sensitive to Olaparib therapy.…”

Section: Discussionsupporting

confidence: 91%

Targeting PARP1 in XRCC1-Deficient Sporadic Invasive Breast Cancer or Preinvasive Ductal Carcinoma In Situ Induces Synthetic Lethality and Chemoprevention

et al. 2018

View full text Add to dashboard Cite

Targeting PARP1 for synthetic lethality is a new strategy for breast cancers harboring germline mutations in BRCA. However, these mutations are rare, and reactivation of BRCA-mediated pathways may result in eventual resistance to PARP1 inhibitor therapy. Alternative synthetic lethality approaches targeting more common sporadic breast cancers and preinvasive ductal carcinoma in situ (DCIS) are desirable. Here we show that downregulation of XRCC1, which interacts with PARP1 and coordinates base excision repair, is an early event in human breast cancer pathogenesis. XRCC1-deficient DCIS were aggressive and associated with increased risk of local recurrence. Human invasive breast cancers deficient in XRCC1 and expres-sing high PARP1 levels also manifested aggressive features and poor outcome. The PARP1 inhibitor olaparib was synthetically lethal in XRCC1-deficient DCIS and invasive breast cancer cells. We conclude that targeting PARP1 is an attractive strategy for synthetic lethality and chemoprevention in XRCC1-deficient breast cancers, including preinvasive DCIS.Significance: These findings show that loss of XRCC1, which is associated with more malignant DCIS, can be exploited by PARP inhibition, suggesting its application as a promising therapeutic and chemoprevention strategy in XRCC1-deficient tumor cells. Cancer Res; 78(24); 6818-27. Ó2018 AACR.

show abstract

Section: Discussionsupporting

confidence: 91%

Targeting PARP1 in XRCC1-Deficient Sporadic Invasive Breast Cancer or Preinvasive Ductal Carcinoma In Situ Induces Synthetic Lethality and Chemoprevention

et al. 2018

View full text Add to dashboard Cite

show abstract

“…In previous studies investigating the expression of XRCC1 in tumors diagnosed at different anatomical sites such as those of Sultana et al 35 in breast cancer and Liu et al 36 in clear cell renal cell carcinoma, low expression of this protein was associated with more aggressive tumors, more advanced stages, higher rates of lymph node metastases, and poor survival. The authors concluded that deficient XRCC1 expression can be used as a prognostic biomarker for these carcinomas.…”

Section: Discussionmentioning

confidence: 91%

Immunohistochemical expression of DNA repair proteins in oral tongue and lower lip squamous cell carcinoma

et al. 2020

View full text Add to dashboard Cite

The DNA repair system involves genes and proteins that are essential for the maintenance of genome integrity and the consequent control of various cellular processes. Alterations in these genes and proteins play a role in tumor development and progression and might be associated with prognosis. The aims of this study were to analyze the immunoexpression of two DNA repair proteins, XPF and XRCC1, in lower lip squamous cell carcinoma (LLSCC) and oral tongue squamous cell carcinoma (OTSCC), and to investigate possible associations with clinical and histopathological parameters. The immunohistochemical expression of XPF and XRCC1 was analyzed semi-quantitatively in 40 cases each of LLSCC and OTSCC. The chi-squared test or Fisher's exact test, when appropriate, was used to investigate the association between expression of the proteins and clinicopathological characteristics. The cytoplasmic immunoexpression of XPF was high in OTSCC (95% of the cases analyzed) but low in LLSCC (52.5%). Among the clinicopathological parameters evaluated, a statistically significant association was observed between high nuclear expression of XRCC1 and the absence of regional lymph node metastasis in patients diagnosed with OTSCC (p=0.006). The high protein expression of XPF and XRCC1 in OTSCC and LLSCC suggests an important role in the development and progression of these tumors. Our study found an association between high nuclear expression of XRCC1 and the absence of loco-regional metastasis in cases diagnosed as OTSCC, suggesting a role of this protein in tumor progression.

show abstract

“…8a , H22 cell migration was significantly inhibited by PFEE-C and PFEE-W treatment in dose-dependent manner (p < 0.001). Matrix metalloproteinase (MMP) family plays a critical role in the migration of tumor cells 25 . After PFEE-C and PFEE-W treatment for 24 h, the levels of MMP-2 and MMP-9 were significantly decreased (p < 0.05, Fig.…”

Section: Resultsmentioning

confidence: 99%

Cultivated and wild Pleurotus ferulae ethanol extracts inhibit hepatocellular carcinoma cell growth via inducing endoplasmic reticulum stress- and mitochondria-dependent apoptosis

Yuan

Wei

et al. 2018

Sci Rep

View full text Add to dashboard Cite

Pleurotus ferulae is a kind of editable mushroom and has various biological functions such as antitumor, antioxidation and immunoregulation. Wild P. ferulae was successfully domesticated but the antitumor function and mechanisms of cultivated and wild P. ferulae need to be compared and explored. Here, we prepared cultivated and wild P. ferulae ethanol extracts (PFEE-C and PFEE-W) and compared their antitumor effect on hepatocellular carcinoma. Our data showed that PFEE-C and PFEE-W significantly inhibited the growth of H22 and HepG2 cells through induction of apoptosis. PFEE-W exhibited higher antitumor activity than PFEE-C. Both PFEE-C and PFEE-W induced endoplasmic reticulum (ER) stress characterized by the up-regulated levels of phosphorylated JNK, cleaved caspase-12 and HSP70, and mitochondrial dysfunction characterized by the reduction of mitochondrial membrane potential and the release of cytochrome c, which promoted the cleavage of caspase-3, -7, -9 and PARP. Moreover, PFEE-C and PFEE-W significantly increased ROS generation in H22 cells and suppressed H22 cell migration through reducing the levels of matrix metalloproteinase -2 and -9. Further, PFEE-C inhibited H22 tumor growth in mouse model and improved the survival of tumor mice. These results indicated that PFEE-C and PFEE-W could inhibit hepatocellular carcinoma cell growth through ER stress- and mitochondria-dependent apoptotic pathways.

show abstract

XRCC1 serves as a potential prognostic indicator for clear cell renal cell carcinoma and inhibits its invasion and metastasis through suppressing MMP-2 and MMP-9

Cited by 17 publications

References 19 publications

Targeting PARP1 in XRCC1-Deficient Sporadic Invasive Breast Cancer or Preinvasive Ductal Carcinoma In Situ Induces Synthetic Lethality and Chemoprevention

Targeting PARP1 in XRCC1-Deficient Sporadic Invasive Breast Cancer or Preinvasive Ductal Carcinoma In Situ Induces Synthetic Lethality and Chemoprevention

Immunohistochemical expression of DNA repair proteins in oral tongue and lower lip squamous cell carcinoma

Cultivated and wild Pleurotus ferulae ethanol extracts inhibit hepatocellular carcinoma cell growth via inducing endoplasmic reticulum stress- and mitochondria-dependent apoptosis

Contact Info

Product

Resources

About