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1. chinaXiv:201803.00958 [pdf]

PIK3CA and AKT2 mutations of gastric cancer in China

wenxiang cheng
Subjects: Biology >> Genetics

Mutations in PI3K and/or AKT have been reported in a variety of cancers. This indicates that the two pathways interact to cause cancer. We have therefore investigated their roles in gastric cancer (GC) in China. In our study, exons 9, 18 and 20 of PIK3CA gene and exons 6~14 of AKT2 gene were screened in 10 GC cell lines and 100 advanced primary GC together with matched normal tissues. Denaturing high performance liquid chromatography (DHPLC) and DNA sequencing were used to analyze the mutations in the two genes. Two point mutations in the PIK3CA gene were identified in 4 of 10 GC cell lines and in 4 of 100 GC primary tumors. Two polymorphisms in AKT2 were detected in 19 of 100 GC primary tumors. One point mutation in AKT2 was detected in 1 of 10 GC cell lines and 3 of 100 GC primary tumors, and no hot spot variation was detected. Our results indicate that PIK3CA and AKT2 mutations are found in GC, although not a common event, therefore they might still play an important role in mediating kinase activities towards gastric carcinogenesis.

submitted time 2018-03-16 Hits2448Downloads1230 Comment 0

2. chinaXiv:201605.01275 [pdf]

Myo9b is a key player in SLIT/ROBO-mediated lung tumor suppression

Kong, Ruirui; Wen, Pushuai; Liu, Jianghong; Zhu, Li; Wu, Jane Y.; Yi, Fengshuang; Ren, Jinqi; Feng, Wei; Yi, Fengshuang; Chen, Xiaoping; Wu, Jane Y.; Li, Xiaofei; Nie, Yongzhan; Wu, Kaichun; Fan, Daiming; Zhu, Li; Nie, Yongzhan; Wu, Kaichun; Fan, Daiming; Zhu, Li
Subjects: Biology >> Biophysics

Emerging evidence indicates that the neuronal guidance molecule SLIT plays a role in tumor suppression, as SLIT-encoding genes are inactivated in several types of cancer, including lung cancer; however, it is not clear how SLIT functions in lung cancer. Here, our data show that SLIT inhibits cancer cell migration by activating RhoA and that myosin 9b (Myo9b) is a ROBO-interacting protein that suppresses RhoA activity in lung cancer cells. Structural analyses revealed that the RhoGAP domain of Myo9b contains a unique patch that specifically recognizes RhoA. We also determined that the ROBO Intracellular domain interacts with the Myo9b RhoGAP domain and inhibits its activity; therefore, SLIT-dependent activation of RhoA is mediated by ROBO inhibition of Myo9b. In a murine model, compared with control lung cancer cells, SLIT-expressing cells had a decreased capacity for tumor formation and lung metastasis. Evaluation of human lung cancer and adjacent nontumor tissues revealed that Myo9b is upregulated in the cancer tissue. Moreover, elevated Myo9b expression was associated with lung cancer progression and poor prognosis. Together, our data identify Myo9b as a key player in lung cancer and as a ROBO-interacting protein in what is, to the best of our knowledge, a newly defined SLIT/ROBO/Myo9b/RhoA signaling pathway that restricts lung cancer progression and metastasis. Additionally, our work suggests that targeting the SLIT/ROBO/Myo9b/RhoA pathway has potential as a diagnostic and therapeutic strategy for lung cancer.

submitted time 2016-05-11 Hits1430Downloads792 Comment 0

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