Kindlins and Cancer: Exploring New Frontiers for Treatment

Kindlins can have various therapeutic uses for cancer treatment
Researchers are leveraging Kindlins to assess the activity of cancerous cells. (Representational image: Unsplash)
Researchers are leveraging Kindlins to assess the activity of cancerous cells. (Representational image: Unsplash)
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Cancer occurs when there is uncontrolled growth of abnormal cells, often due to mutations that alter cellular functions. This abnormal cell multiplication can damage healthy cells, potentially leading to organ failure and death. Cancer is generally classified into two types:

1. Benign: These tumors are easier to treat and can often be managed with surgery or chemotherapy.

2. Malignant: These cancerous cells can spread throughout the body via the bloodstream or lymphatic system, damaging and mutating healthy cells.

For many years, cancer was considered incurable and often fatal. However, advancements in technology and research have led to the development of various drugs and surgical procedures that can nearly eradicate cancer and prevent its recurrence.

Cancer treatment depends on the type, stage, location, and overall health of the patient. The primary treatment options include:

Surgery: Often the first line of treatment for many types of cancer, especially solid tumors. The goal is to remove as much of the tumor as possible. Techniques range from curative surgery, which aims to remove the entire tumor, to debulking surgery, which removes a portion of the tumor when full removal might be too damaging.

Radiation Therapy: This uses high-energy particles or waves to destroy or damage cancer cells and can be used alone or in combination with other treatments.

Chemotherapy: Involves the use of drugs to kill cancer cells or stop them from growing and dividing. These drugs can be administered intravenously, orally, or directly into a specific area of the body. T

In the quest to find new treatments, research has focused on understanding the role of Kindlins—adapter proteins present in the cells of vertebrates—in cancer therapy. These proteins are involved in various signaling pathways, making them potential targets for cancer treatment. Kindlins function by converting extracellular mechanical cues into biochemical signals inside the cells and facilitate the transmission of these signals by interacting with structural proteins, receptors, and transcription factors, thus triggering a cascade of chemical signals within the cell.

Disruptions in the structure of these proteins can affect mechanochemical signaling and disturb the body's overall balance, which is crucial for survival. Mutations in Kindlins can occur due to various factors, such as exposure to chemicals, carcinogens like nicotine, and ultraviolet rays. Understanding the reasons behind these mutations could lead to insights into the growth of cancer cells.

Researchers from the S. N. Bose National Centre for Basic Sciences in Kolkata, an autonomous institute under the Department of Science and Technology (DST), collected data on 10,000 patients across 33 types of cancer from The Cancer Genome Atlas. Their aim was to study the role of Kindlins in the transformation of normal cells into cancerous ones. The team, led by Debojyoti Chowdhury and guided by Prof. Shubhasis Haldar, found that Kindlin 1, a member of the Kindlin family, plays a role in regulating the immune microenvironment in breast cancer. They also discovered that cancer-specific metabolic processes, such as the TCA cycle and glycolysis, are influenced by Kindlin 2.

The association of alterations in kindlin family proteins with 10 hallmarks of cancer
The association of alterations in kindlin family proteins with 10 hallmarks of cancer

By studying all Kindlin family members collectively, we can gain a comprehensive understanding of their potential complementary and synergistic roles in cancer biology. This includes examining the interaction of different Kindlin proteins with each other or with other cellular components to influence cancer cell behavior, tumor progression, and response to therapy

Debojyoti Chowdhury, Lead Researcher

The Kindlin family consists of three members: Kindlin 1, 2, and 3, each with distinct amino acid sequences and tissue distributions. Cancer cells can use the Hippo signaling pathway to migrate and invade other tissues, and Kindlin 2 is also involved in this signaling pathway.

Using structural and functional genomic tools, the researchers explored the role of Kindlin family proteins in mechanochemical signaling across various cancers. The study revealed the role of Kindlins in tumor progression, metastasis, and epithelial-mesenchymal transition (EMT). This structural genomics approach identified links with clinical parameters, providing evidence for the potential mechanochemical significance of Kindlins across different stages and subtypes of cancer.

Epithelial-mesenchymal transition (EMT)
In EMT, cells shift from being more like tightly packed, organized epithelial cells (like those lining our skin) to becoming more free-moving and flexible mesenchymal cells (like those in our muscles). This process happens when cancer cells spread to different parts of the body

The data related to Kindlin family alternations and mutational and stability analyses presented in our work strongly coincide with those of previous experimental studies. We found that Kindlin 2 expression is elevated in breast cancer, and it activates epithelial-mesenchymal transition (EMT)

Debojyoti Chowdhury, Lead Researcher

The study, published in the journal Communications Biology, has provided a deeper understanding of the complex interactions between tumors and their microenvironment. It highlighted the potential of Kindlins as promising targets for innovative mechano-modulatory cancer therapies, offering context-specific options for intervention and treatment strategies.

Chemoresistance and tumor relapse are significant challenges for oncologists. This research will serve as a beacon for developing future therapeutic strategies targeting the roles of Kindlins in cancer treatment. It represents a new strategy in the centuries-old battle against cancer.

Reference :

1. Study of Kindlins reveal novel pathways to cancer treatment. (n.d.). https://pib.gov.in/PressReleasePage.aspx?PRID=2039090

2. Rognoni, E., Ruppert, R., & Fässler, R. (2016). The kindlin family: functions, signaling properties and implications for human disease. Journal of Cell Science129(1), 17–27. https://doi.org/10.1242/jcs.161190

3. What Is Cancer? (2021b, October 11). Cancer.gov. https://www.cancer.gov/about-cancer/understanding/what-is-cancer

(Input from various source)

(Rehash /Yash Kamble/MSM)

Researchers are leveraging Kindlins to assess the activity of cancerous cells. (Representational image: Unsplash)
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