The Src Kinase, cell communication & growth control

Src 激酶，细胞通讯

• 批准号: 7109343
• 负责人: GARY S GOLDBERG
• 金额: $ 21.64万
• 依托单位: UNIV OF MED/DENT NJ-SCH OSTEOPATHIC MED
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-08 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7109343
• 关键词: biological signal transduction; cell growth regulation; cell transformation; electrical conductance; enzyme activity; fluorescent dye /probe; gap junctions; gene expression; immunofluorescence technique; intercellular connection; membrane channels; microarray technology; mitogen activated protein kinase; mixed tissue /cell culture; neoplastic cell; protein kinase; transfection; voltage /patch clamp

DESCRIPTION (provided by applicant): Tumor cell growth can be controlled by surrounding normal cells. This process is called "heterologous growth control". The goal of this project is to elucidate mechanisms underlying this process. We will determine how nontransformed cells affect the Src signaling cascade in neighboring transformed cells. The need for heterologous gap junctional communication in heterologous growth control will be evaluated in Specific Aim 1. We hypothesize that nontransformed cells do not need to form active gap junction channels with Src transformed cells to normalize their growth. We will utilize connexin knockout cells, chemical blockers or antisense nucleic acids to suppress gap junctional communication. Intercellular communication will be examined by the transfer of fluorescent dyes, endogenous metabolites, and electrical conductance. If heterologous growth control occurs in the absence of gap junctional communication, then, as we hypothesize, gap junctional communication is not required for heterologous growth control. Effects of nontransformed cells on the Src kinase activity, and the activity of kinases acting downstream of Src, in Src transformed cells will be evaluated in Specific Aims 2 and 3, respectively. We hypothesize that nontransformed cells quell Src kinase activity, and affect the activity of downstream kinases, in neighboring transformed cells. We will use novel techniques that we have developed to examine kinase activity in transformed cells that are morphologically reversed to a normal phenotype by neighboring nontransformed cells. Our hypothesis will be proven if the Src signaling in transformed cells cascade is blocked by communication with nontransformed cells. Effects of nontransformed cells on the global expression pattern of genes in neighboring transformed cells will be examined in Specific Aim 4. We hypothesize that nontransformed cells alter the expression of specific genes in neighboring transformed cells. We will utilize DNA chips to compare the gene profiles of transformed cells cocultured with nontransformed cells to transformed cells and nontransformed cells grown alone. The hypothesis will be proven if the expression levels of some genes, but not others, in transformed cells are affected by contact with nontransformed cells during heterologous growth control.

描述（由申请人提供）：肿瘤细胞生长可由周围正常细胞控制。这个过程被称为“异源生长控制”。 本项目的目标是阐明这一过程的机制。我们将确定非转化细胞如何影响邻近转化细胞中的Src信号级联。 将在特定目标1中评价异源生长控制中对异源间隙连接通讯的需求。 我们假设，非转化细胞不需要形成活性间隙连接通道与Src转化细胞正常化其生长。 我们将利用连接蛋白敲除细胞、化学阻断剂或反义核酸来抑制间隙连接通讯。 将通过荧光染料、内源性代谢物和电导的转移来检查细胞间通讯。 如果异源生长控制发生在缺乏间隙连接通讯，然后，我们假设，间隙连接通讯是不需要异源生长控制。 将分别在特定目的2和3中评价非转化细胞对Src转化细胞中Src激酶活性和Src下游作用激酶活性的影响。我们假设，非转化细胞平息Src激酶活性，并影响下游激酶的活性，在邻近的转化细胞。 我们将使用我们已经开发的新技术来检查转化细胞中的激酶活性，这些转化细胞在形态上被邻近的非转化细胞逆转为正常表型。如果转化细胞级联中的Src信号被与非转化细胞的通讯阻断，我们的假设将得到证明。 非转化细胞对邻近转化细胞中基因整体表达模式的影响将在具体目标4中进行检查。 我们假设非转化细胞改变了邻近转化细胞中特定基因的表达。 我们将利用DNA芯片比较与非转化细胞共培养的转化细胞与单独生长的转化细胞和非转化细胞的基因谱。 如果在异源生长控制过程中，转化细胞中某些基因的表达水平受到与非转化细胞接触的影响，而其他基因的表达水平不受影响，则该假设将得到证明。

项目成果

Full length and delta lactoferrin display differential cell localization dynamics, but do not act as tumor markers or significantly affect the expression of other genes.

• DOI: 10.2174/1573406053402532
• 发表时间: 2005-01-01
• 期刊: Medicinal chemistry (Shariqah (United Arab Emirates))
• 作者: Goldberg, Gary S;Kunimoto, Takehiko;Tsuda, Hiroyuki
• 通讯作者: Tsuda, Hiroyuki

Src activates Abl to augment Robo1 expression in order to promote tumor cell migration.

Src 激活 Abl 增强 Robo1 表达，从而促进肿瘤细胞迁移。

• DOI: 10.18632/oncotarget.100710
• 发表时间: 2010
• 期刊: Oncotarget
• 作者: Khusial,PRaaj;Vadla,Bhaskar;Krishnan,Harini;Ramlall,TrudyF;Shen,Yongquan;Ichikawa,Hitoshi;Geng,Jian-Guo;Goldberg,GaryS
• 通讯作者: Goldberg,GaryS