食管鳞癌发病和死亡率高，淋巴结转移机制未明。近期研究发现，牙龈卟啉单胞菌（Pg）在食管鳞癌组织中富集，和淋巴结转移程度正相关，然其分子机制尚不明确。我们预实验显示：Pg通过β1整合素选择性感染食管鳞癌细胞并增强其迁移能力；进一步地，Pg诱导CD151表达上调，CD151和β1整合素形成复合体并参与介导Pg感染和宿主细胞迁移。据此我们提出科学假说：Pg通过β1整合素识别食管鳞癌细胞，诱导CD151激活放大β1整合素信号通路，促进Pg感染和细胞迁移。为此，我们拟进一步：明确Pg在食管鳞癌组织中选择性定植的分子机制；分析Pg如何诱导CD151表达上调；探讨CD151在Pg感染和Pg激活β1整合素信号通路中的双重调节作用；验证β1整合素/CD151信号通路作为食管鳞癌淋巴结转移治疗靶点的可行性。项目的开展有望揭示Pg感染在食管鳞癌淋巴结转移中的作用及其可能分子机制，为寻找新的治疗靶点提供理论依据。

Esophageal squamous cell carcinoma (ESCC) is highly metastatic, with the underlying mechanisms remained to be explored. Recent research has shown that Porphyromonas gingivalis (P. gingivalis), a major pathogen for periodontal disease, is present in ESCC tissues and associated with ESCC lymph node metastasis status. However, the underlying mechanisms of the colonization of P. gingivalis and its mode of action in ESCC metastasis have not been well studied. Our preliminary results showed that, as compared with normal esophageal epithelial cells, P. gingivalis preferentially invades ESCC cells and promotes cell migration, probably via overexpressed β1 integrins in ESCC cells. Next, we sought to investigate the underlying mechanism and identify the key host regulator of β1 integrin signaling activated by P. gingivalis infection. Interestingly, we found that P. gingivalis infection upregulates CD151 expression in ESCC cells. As an integrin partner, CD151 has proven to be indispensable for integrins outside-in and inside-out signaling, as well as integrin intracellular trafficking. Moreover, CD151 might act as a “co-receptor” for pathogen infection through its cooperation with the primary receptors such as integrins. In this consideration, we propose that CD151 might have dual effects in the regulation of P. gingivalis invasion and P. gingivalis-mediated tumor cell migration, probably by its crosstalk with β1 integrin signaling. In support of this, we showed that CD151 is overexpressed in ESCC tissue and correlates with β1 integrin expression. In ESCC cells, CD151 binds to β1 integrin during P. gingivalis infection, implicating the regulatory role of CD151 in β1 integrin signaling. Furthermore, as expected, CD151 knockdown significantly suppresses P. gingivalis invasion into ESCC cells, as well as P. gingivalis-mediated cell migration. Taken together, we hypothesize that P. gingivalis invades ECSS cells and promotes cell migration via β1 integrins/CD151 signaling. To this end, we intend to further 1) clarify the molecular mechanism of colonization of Pg in ESCC; 2) analyze how Pg induces upregulation of CD151 expression; 3) explore the dual regulatory role of CD151 in Pg invasion and Pg-mediated cell migration through its crosstalk with β1 integrin signaling; and 4) test the feasibility of β1 integrin / CD151 signaling pathway as a therapeutic target for lymph node metastasis of ESCC. This study is expected to reveal the role of Pg infection in lymph node metastasis of ESCC and its possible molecular mechanism, which holds promise for novel target therapeutic strategies.