STIM1在口腔癌細胞的侵襲及放射反應中所扮演的角色

Abstract

To escape from the primary tumor site, metastatic cancer cells acquire the abilities to invade and migrate partially through Ca2+ signaling-regulated cytoskeleton rearrangement and focal adhesion dynamics. To maintain physiological homeostasis, intracellular Ca2+ pool is tightly controlled via store-operated calcium entry (SOCE), which includes the activation of stromal interaction molecules (STIM) upon Ca2+ depletion within the endoplasmic reticulum, followed by the activation of Ca2+-selective channel ORAI on the plasma membrane to replenish Ca2+ from extracellular space. Several studies have revealed aberrant levels of STIM1 in human cancers such as breast cancer, renal cell carcinoma and colorectal cancer, but whether STIM1 aberrancy affects SOCE activities or other signaling pathways to induce cancer cell migration or invasion were still unclear. Our preliminary results indicated that expression levels of STIM1 were associated with the progression of oral cancer. Oral cancer in the domestic prevalence rate is very high, and in the domestic top ten cancers, may have a considerable relationship with the diet culture, of which oral squamous cell carcinoma (OSCC) is one of the most common oral cancer, and prone to cervical lymph node metastasis. At present, the treatment of oral cancer is mainly surgical resection, combined with radiotherapy, but often a certain proportion of patients appear treatment resistance. Therefore, this study is intended to investigate the hypothesis of lymph node metastasis and radiotherapy in oral cancer cells regulated by STIM1. Reduction of SOCE activities targeting STIM1 by shRNA in oral squamous cell carcinoma (OSCC), or over-expressing STIM1 to see whether it affects the proliferation and invasive ability of cancer cells, Immunohistochemical (IHC) staining was used to see the difference of STIM1 in situ carcinoma and metastatic site. We also used the Xenograft mouse models to observe the role of STIM1 in lymph node metastasis and how to influence radiation therapy.