K-ras mutations occur frequently in colon cancer and contribute to autonomous growth. In the azoxymethane (AOM) model of colon cancer, in addition to K-ras mutations, we have shown that wild-type (WT) Ras can be activated by upstream pathways, including, e.g., signaling by ErbB receptors. Tumors with mutant or activated WT Ras had increased cyclooxygenase-2 (Cox-2) expression. We have also show...

Constitutively active RAS small GTPases promote the genesis of human cancers. An important goal in cancer biology is to identify means of countervailing activated RAS signaling to reverse malignant transformation. Oncogenic K-RAS mutations are found in virtually all pancreatic adenocarcinomas, making the RAS pathway an ideal target for therapeutic intervention. How to best contravene hyperactiv...

UNLABELLED H-Ras, K-Ras, and N-Ras regulate cellular growth and survival and are often activated by somatic mutation in human tumors. Although oncogenic lesions occur in a single Ras isoform within individual tumors, it is unclear whether the remaining wild-type isoforms play supporting roles in tumor growth. Here, we show that oncogenic and wild-type Ras isoforms play independent and nonredund...

R-Ras has a high degree of sequence homology with Ras and other members of the Ras subfamily, including Rap, TC21, and M-Ras. Although R-Ras has been suggested to regulate cell adhesion, migration, and invasion, the biological mechanism has not been well assessed. In this report, we show that constitutively active R-Ras (38V) induces a more rounded cell shape and redistribution of focal adhesio...

Activating K-ras mutations are found in approximately 90% of pancreatic carcinomas and may contribute to the poor prognosis of these tumors. Because radiotherapy is frequently used in pancreatic cancer treatment, we assessed the contribution of oncogenic K-ras signaling to pancreatic cancer radiosensitivity. Seven human pancreatic carcinoma lines with activated K-ras and two cell lines with wil...

The Ras oncoprotein is a key driver of cancer. However, Ras also provokes senescence, which serves as a major barrier to Ras-driven transformation. Ras senescence pathways remain poorly characterized. NORE1A is a novel Ras effector that serves as a tumor suppressor. It is frequently inactivated in tumors. We show that NORE1A is a powerful Ras senescence effector and that down-regulation of NORE...

K-Ras and H-Ras share identical effectors and have similar properties; however, the high degree of tumor-type specificity associated with K-Ras and H-Ras mutations suggests that they have unique roles in oncogenesis. Here, we report that oncogenic K-Ras, but not H-Ras, suppresses non-canonical Wnt/Ca(2+) signaling, an effect that contributes strongly to its tumorigenic properties. K-Ras does th...

The renin-angiotensin system (RAS) has mainly been categorized as a circulating and a local tissue RAS. A new component of the local system, known as the intracellular RAS, has recently been described. The intracellular RAS is defined as synthesis and action of ANG II intracellularly. This RAS appears to differ from the circulating and the local RAS, in terms of components and the mechanism of ...

Activating mutations of RAS frequently occur in subsets of human cancers, indicating that RAS activation is important for tumorigenesis. However, a large proportion of these cancers still retain wild-type RAS alleles, suggesting that either the RAS pathway is activated in a distinct manner or another pathway is deregulated. To uncover novel tumor-suppressor genes, we screened an RNA-interferenc...

CONTEXT Ras gene mutations have been associated to a wide range of human solid tumors. Members of the ras gene family (Ki-ras, Ha-ras and N-ras) are structurally related and code for a protein (p21) known to play an important role in the regulation of normal signal transduction and cell growth. The frequency of ras mutations is different from one type of tumor to another, suggesting that point ...