Normal Cells Control the Growth of Neighboring Transformed Cells Independent of Gap Junctional Communication and Src Activity

Alexander, David B.; Ichikawa, Hitoshi; Bechberger, John F.; Valiūnas, Virginijus; Ohki, Misao; Naus, Christian C.; Kunimoto, Takehiko; Tsuda, Hiroyuki; Miller, W. Todd; Goldberg, Gary S.

doi:10.1158/0008-5472.can-03-2558

Cited by 61 publications

(100 citation statements)

References 61 publications

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“…Working with the same v-src-transformation system, Alexander et al (46) showed that the suppression of transformed cell growth by neighboring nontransformed cells required direct physical contact; communication by diffusible factors was not sufficient. Importantly, the src-kinase activity of the transformed cells was not inhibited by the contact with the nontransformed cells.…”

Section: Intercellular Surveillance (Microenvironmental Control)mentioning

confidence: 99%

Toward a genetics of cancer resistance

Klein

2009

Proc. Natl. Acad. Sci. U.S.A.

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Two of three humans never get cancer. Even the majority of heavy smokers remain cancer free. Is this a matter of chance, or are there cancer-resistant genotypes? Based on the evidence discussed, it would appear that evolution has favored a limited number of relatively common resistance genes that may nip incipient cancerous foci in the bud, i.e., to stop them at their inception. It is further suggested that resistance genes may act at the level of tissue organization in a dominant fashion.

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Section: Intercellular Surveillance (Microenvironmental Control)mentioning

confidence: 99%

Toward a genetics of cancer resistance

Klein

2009

Proc. Natl. Acad. Sci. U.S.A.

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“…90,91 Some of these genes encode factors that promote cell migration. For example, Src induces the expression of Slit2.…”

Section: Src and Robo1mentioning

confidence: 99%

“…For example, Src induces the expression of Slit2. 90 Slit2 is a secreted protein that binds to a receptor called "Robo1." 92,93 Robo1 is a transmembrane receptor of the immunoglobulin family.…”

Section: Src and Robo1mentioning

confidence: 99%

“…110,111 Cells transformed by chemicals, tumor viruses, and oncogenes such as Src can be normalized by contact with nontransformed cells. 90,[112][113][114] This suppression of the neoplastic phenotype by direct contact between transformed and nontransformed cells is called contact normalization.…”

Section: Contact Normalizationmentioning

confidence: 99%

“…[120][121][122][123] However, studies indicate that gap junctions are not required for contact normalization. 90,106 Nonetheless they may augment the ability of normal cells to control the growth of neighboring tumor cells. 121,[124][125][126] The presence of several adhesion molecules, including connexins and cadherins, on the cell surface may help maintain normal cell phenotypes and safeguard against malignancies.…”

Section: Contact Normalizationmentioning

confidence: 99%

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Src Points the Way to Biomarkers and Chemotherapeutic Targets

Krishnan¹,

Miller

Goldberg³

2012

Genes & Cancer

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The role of Src in tumorigenesis has been extensively studied since the work of Peyton Rous over a hundred years ago. Src is a non-receptor tyrosine kinase that plays key roles in signaling pathways controlling tumor cell growth and migration. Src regulates the activities of numerous molecules to induce cell transformation. However, transformed cells do not always migrate and realize their tumorigenic potential. They can be normalized by surrounding nontransformed cells by a process called contact normalization. Tumor cells need to override contact normalization to become malignant or metastatic. In this review, we discuss the role of Src in cell migration and contact normalization, with emphasis on Cas and Abl pathways. This paradigm illuminates several chemotherapeutic targets and may lead to the identification of new biomarkers and the development of effective anticancer treatments.

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What keeps cells in tissues behaving normally in the face of myriad mutations?

Rubin

2006

BioEssays

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SummaryThe use of a reporter gene in transgenic mice indicates that there are many local mutations and large genomic rearrangements per somatic cell that accumulate with age at different rates per organ and without visible effects. Dissociation of the cells for monolayer culture brings out great heterogeneity of size and loss of function among cells that presumably reflect genetic and epigenetic differences among the cells, but are masked in organized tissue. The regulatory power of a mass of contiguous normal cells is expressed in its capacity to normalize the appearance and growth behavior of solitary homophilic neoplastic cells, and to redirect differentiation of solitary heterophilic stem-like cells. Intimate contact between the interacting cells is required to induce these changes. The normalization of the neoplastic phenotype does not require gap junctional communication between cells, though transdifferentiation might. These varied relationships are manifestations of the unifying biological principle of ''order in the large over heterogeneity in the small''.

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Normal Cells Control the Growth of Neighboring Transformed Cells Independent of Gap Junctional Communication and Src Activity

Cited by 61 publications

References 61 publications

Toward a genetics of cancer resistance

Toward a genetics of cancer resistance

Src Points the Way to Biomarkers and Chemotherapeutic Targets

What keeps cells in tissues behaving normally in the face of myriad mutations?

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