A new study examined the effects of Kindlins – an adaptor protein found inside vertebrate cells – on various types of cancer. Since this protein is central to many signaling pathways, targeting it could lead to new cancer treatments that can quickly address many aspects of the disease.
Kindlins are adaptor proteins that are present within the cell membranes of almost all cell types in vertebrates. They transduce extracellular mechanical signals to biochemical signals within cells and play a critical role in the transmission of extracellular signals by naturally interacting with structural proteins, receptors, and transcription factors, thereby initiating a cascade of chemical signals within the cell.
Structural disruptions in these proteins can have widespread effects on mechanochemical signaling, disrupting the state of balance between all physiological systems needed for the body to survive and function properly. This balanced state of the body is called homeostasis.
Kindlins can undergo permanent alterations under the influence of numerous chemical and physical carcinogens such as nicotine, ultraviolet rays and many others. Such alterations can potentially disturb the universal mechanical homeostasis within cells. Understanding the consequences of genetic alterations in kindlins may therefore prove to be the key to unraveling the complex mechanisms of growth in cancer cells.
A team from S.N. Bose National Centre for Basic Sciences, an autonomous institute of the Department of Science and Technology (DST), Kolkata, collected data from 10,000 patients with 33 types of cancer from the Cancer Genome Atlas to understand the role of kindlins in the transformation of normal cells into cancerous cells.
Researchers led by Debjyoti Chowdhury, working under the guidance of Professor Shubhashish Haldar, found that Kindlin-1 (belongs to the Kindlin family) regulates the dysfunctional microenvironment in breast cancer and that regulation of cancer-specific metabolism (chemical processes in living bodies that sustain life), such as the TCA cycle and glycolysis, is controlled by Kindlin-2.
Debjyoti Chowdhury said that the Kindlin family of proteins consists of three members: Kindlin 1, 2, 3, which have different amino acid sequences and tissue distribution. “Hippo signaling is a type of signal in cancer cells that tells the cell to migrate and invade other tissues. Kindlin-2 can also regulate Hippo signaling.”