| Autor: |
Moeez Rathore, Michel’le Wright, Rajat Bhattacharya, Fan Fan, Ali Vaziri-Gohar, Jordan Winter, Zhenghe Wang, Sanford D Markowitz, Joseph Willis, Lee M. Ellis, Rui Wang |
| Rok vydání: |
2021 |
| Předmět: |
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| DOI: |
10.1101/2021.04.27.441690 |
| Popis: |
We previously showed that liver endothelial cells (ECs) secreted soluble factors in a paracrine fashion and activated human epidermal growth factor receptor 3 (HER3, also known as ERBB3) for promoting colorectal cancer (CRC) growth and chemoresistance. However, RAS proteins play a critical role in receptor tyrosine kinase signaling pathways, and KRAS mutations mediate CRC resistance to therapies targeting EGFR, another HER protein. Therefore, the role of KRAS mutation status in EC-induced HER3 activation and CRC survival was investigated as it has therapeutic implications. We used CRC cell lines and patient-derived xenografts harboring KRAS wild-type or mutant genes and demonstrated that liver EC-secreted factors promoted HER3-mediated CRC cell growth independent of KRAS mutation status. Also, blocking HER3 in CRC cells by siRNAs or a HER3 antibody seribantumab blocked EC-induced CRC survival. Our findings highlight the potential of utilizing HER3 targeted therapies for treating patients with mCRC independent of RAS mutational status. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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