Abstract
Cancer stem-like cells (CSCs) have been reported to play major roles in tumorigenesis, tumor relapse, and metastasis after therapy against colorectal carcinoma (CRC). Therefore, identification of colorectal CSC regulators could provide promising targets for CRC. Ligand-of-Numb protein X1 (LNX1) is one E3 ubiquitin ligase which mediates the ubiquitination and degradation of Numb. Although several studies indicate LNX1 could be a potential suppressor of cancer diseases, the functions of LNX1 in mediating cancer stemness remain poorly understood. In this study, LNX1 was identified as a negative regulator of cancer stemness in CRC, which was downregulated in colonospheres or side population (SP) cells. Furthermore, the coxsackievirus and adenovirus receptor (CXADR) was found to be one critical downstream mediator of cancer stemness regulated by LNX1. Interestingly, the anti-breast cancer drug tamoxifen was found to be an agonist of LNX1 and suppress cancer stemness in CRC. In sum, this study provided the evidences that LNX1 signaling plays important roles in regulating the stemness of colon cancer cells.
Highlights
As one of the most commonly diagnosed cancer diseases in both men and women, colorectal carcinoma (CRC) has caused serious concerns demographically and economically throughout the world
There has been a rapid advancement in the field of cancer stem-like cells (CSCs) research in colorectal carcinoma which has provided enough room for the application of more reliable cancer therapies [36]
By exploring the underlying molecular mechanisms, it was found that Ligandof-Numb protein X1 (LNX1) suppresses cancer stemness which partially requires the coxsackievirus and adenovirus receptor (CXADR) interference in colorectal carcinoma
Summary
As one of the most commonly diagnosed cancer diseases in both men and women, colorectal carcinoma (CRC) has caused serious concerns demographically and economically throughout the world. There are 95,270 cases of CRC and 49,190 deaths in the US in 2016 whereas in China, almost 376,000 patients were diagnosed with CRC and 191,000 of both genders died of CRC in 2015 [1]. With the occurrence of chemoresistance and tumor relapse after therapy, the frontier of cancer stemness has become the focus of recent developments in CRC research [2,3]. Plethora of research reports have demonstrated that there is a small group of cells named as cancer stem-like cells (CSCs) possessing the ability of self-renewal and higher proliferation rate with increased capacity of invasion, metastasis and tumor formation [4,5,6].
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