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Nakamichi, K.

Publications and source records attributed to Nakamichi, K..

2 recordsLinked to original sources

Metastatic potentials classified with hypoxia-inducible factor 1 downstream gene in pan-cancer cell lines

Hypoxia-inducible factor 1 (HIF1) gene codes a transcription factor that is stabilized under hypoxia conditions via post-translational modifications. HIF1 regulates tumor malignancy and metastasis by gene transcriptions, such as Warburg effect- and angiogenesis-related genes, in cancer cells. However, the HIF1 downstream genes show varied expressional patterns in different cancer types. Herein, we performed the hierarchical clustering based on the HIF1 downstream gene expression patterns using 1,406 cancer cell lines crossing 30 types of cancer to understand the relationship between HIF1 downstream genes and the metastatic potential of cancer cell lines. Four types of cancer were classified by HIF1 downstream genes with significantly altered metastatic potentials. Furthermore, different HIF1 downstream gene subsets were extracted to discriminate each subtype for the four cancer types. HIF1 downstream subtyping classification will help understand the novel insight into tumor malignancy and metastasis in each cancer type. FundingThis work was supported by Project for JSPS KAKENHI (Grant-in-Aid for Scientific Research (C): JP23K06665 to JN, Grant-in-Aid for Early-Carrier Scientists: JP21K15562 to JN), and in part by translational research program from Fukushima Prefecture (KS). Competing Interests statementThe authors have declared that no conflict of interest exists.

cancer biology↗

Targeting c-Jun is a potential therapy of luminal breast cancer bone metastasis

Luminal breast cancer has the highest bone metastasis frequency among all breast cancer subtypes, but its metastatic mechanism has not been elucidated because of the lack of appropriate metastatic cell lines. The study aim was to characterize high-osteolytic bone metastatic MCF7-BM cell lines and extract c-Jun, a novel bone metastasis marker. We found that c-Jun was upregulated in MCF7-BM cells, and its deficiency was associated with suppression of the cell migration, transformation, and stemness of BM cells. In vivo, c-Jun-deficient MCF7-TAM67 cells exhibited weaker bone metastatic ability. Additionally, c-Jun overexpression in MCF7-BM cells led to a tumor-migration promotion cycle in the bone microenvironment possibly by enhancing calcium-induced migration and releasing the osteoclast activator BMP5. Inhibition of c-Jun by JNK-IN-8, a JNK inhibitor, effectively reduced tumorigenesis activities and bone metastatic tumors. Our results indicate the potential benefits of a therapy that targets c-Jun to prevent or minimize luminal breast cancer bone metastasis.

cancer biology↗